Acetic Acid → (2S,6S)-6-((2R,3R)-3-(benzyloxymethoxy)-2-(tert-butyldimethylsilyloxy)butyl)-2-((E)-4-((2R,6S)-6-(((2R,6S)-6-((S)-4-hydroxy-2-(4-methoxybenzyloxyl)butyl)-4-methylene-tetrahydro-2H-pyran-2-yl)methyl)-4-methylene-tetrahydro-2H-pyran-2-yl)-2-methylbut-3-en-2-yl)-2-methoxy-dihydro-2H-pyran-3(4H)-one

HRID 509210Notes

Reaction equation

HRID 509210 reaction equation
[CH2:1]([O:8][CH2:9][O:10][C@H:11]([CH3:83])[C@H:12]([O:75][Si:76]([C:79]([CH3:82])([CH3:81])[CH3:80])([CH3:78])[CH3:77])[CH2:13][C@H:14]1[O:19][C@:18]([C:22]([CH3:73])(/[CH:24]=[CH:25]/[C@H:26]2[CH2:31][C:30](=[CH2:32])[CH2:29][C@@H:28]([CH2:33][C@H:34]3[CH2:39][C:38](=[CH2:40])[CH2:37][C@@H:36]([CH2:41][C@@H:42]([O:63][CH2:64][C:65]4[CH:70]=[CH:69][C:68]([O:71][CH3:72])=[CH:67][CH:66]=4)[CH2:43][CH2:44][O:45][Si](C(C)(C)C)(C4C=CC=CC=4)C4C=CC=CC=4)[O:35]3)[O:27]2)[CH3:23])([O:20][CH3:21])[C:17](=[O:74])[CH2:16][CH2:15]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CCCC[N+](CCCC)(CCCC)CCCC.[F-].C1COCC1.CC(O)=O>CN(C=O)C>[CH2:1]([O:8][CH2:9][O:10][C@H:11]([CH3:83])[C@H:12]([O:75][Si:76]([C:79]([CH3:82])([CH3:81])[CH3:80])([CH3:77])[CH3:78])[CH2:13][C@H:14]1[O:19][C@:18]([C:22]([CH3:73])(/[CH:24]=[CH:25]/[C@H:26]2[CH2:31][C:30](=[CH2:32])[CH2:29][C@@H:28]([CH2:33][C@H:34]3[CH2:39][C:38](=[CH2:40])[CH2:37][C@@H:36]([CH2:41][C@@H:42]([O:63][CH2:64][C:65]4[CH:70]=[CH:69][C:68]([O:71][CH3:72])=[CH:67][CH:66]=4)[CH2:43][CH2:44][OH:45])[O:35]3)[O:27]2)[CH3:23])([O:20][CH3:21])[C:17](=[O:74])[CH2:16][CH2:15]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 8028TetrahydrofuranHCID 2724141Tetrabutylammonium FluorideHCID 131733237(2S,6S)-6-((2R,3R)-3-(benzyloxymethoxy)-2-(tert-butyldimethylsilyloxy)butyl)-2-((E)-4-((2R,6S)-6-(((2R,6S)-6-((S)-4-(tert-butyldiphenylsilyloxy)-2-(4-methoxybenzyloxyl)butyl)-4-methylene-tetrahydro-2H-pyran-2-yl)methyl)-4-methylene-tetrahydro-2H-pyran-2-yl)-2-methylbut-3-en-2-yl)-2-methoxy-dihydro-2H-pyran-3(4H)-one

Product 1

HCID 131733238(2S,6S)-6-((2R,3R)-3-(benzyloxymethoxy)-2-(tert-butyldimethylsilyloxy)butyl)-2-((E)-4-((2R,6S)-6-(((2R,6S)-6-((S)-4-hydroxy-2-(4-methoxybenzyloxyl)butyl)-4-methylene-tetrahydro-2H-pyran-2-yl)methyl)-4-methylene-tetrahydro-2H-pyran-2-yl)-2-methylbut-3-en-2-yl)-2-methoxy-dihydro-2H-pyran-3(4H)-oneYield 90.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Procedure

To stirring solution of TBDPS ether 7 (119 mg, 0.101 mmol, 1.0 equiv) in DMF, was added a solution containing 1.0 M TBAF in THF (101 μL, 0.101 mmol, 1.0 equiv), and 1.0 M AcOH in DMF (101 μL, 0.101 mmol, 1.0 equiv) in additional DMF (300 μL), via cannula, rinsing once with DMF (300 μL). Stirring continued at rt for 21 h, and the reaction mixture was diluted with 40% EtOAc/hexanes (5 mL) and quenched with water (5 mL). The phases were separated and the aqueous phase was extracted three times with 40% EtOAc/hexanes (5 mL). The combined organic phases were dried over Na2SO4, filtered, and concentrated under reduced pressure. Purification was accomplished using flash column chromatography with a 3×8 cm silica gel column, eluting with 30% EtOAc/hexanes, collecting 13×100 mm test tube fractions. The product containing fractions (6-35) were combined and concentrated under reduced pressure to provide pure alcohol 22 (85.2 mg, 90%) as a clear viscous oil: Rf=0.21 (30% EtOAc/hexanes); [α]D20=+3.1 (c=1.03, CHCl3); 500 MHz 1H NMR (CDCl3) δ 7.38-7.24 (m, 7H), 6.88 (d, J=8.3 Hz, 2H), 6.04 (d, J=16.1 Hz, 1H), 5.46 (dd, J=16.1 6.3, Hz, 1H), 4.80 (d, J=6.8 Hz, 1H), 4.78 (d, J=6.8 Hz, 1H), 4.73 (d, J=1.5 Hz, 2H), 4.67 (s, 1H), 4.63 (s, 2H), 4.59 (s, 1H), 4.50 (d, J=10.7 Hz, 1H), 4.46 (d, J=10.7 Hz, 1H), 4.13-4.09 (m, 1H), 4.07 (ddd, J=9.0, 4.1, 2.4 Hz, 1H), 3.91-3.86 (m, 1H), 3.84-3.70 (m, 4H), 3.80 (s, 3H), 3.56-3.42 (m, 3H), 3.29 (s, 3H), 2.44 (dd, J=8.3, 5.9, Hz, 2H), 2.35 (s, 1H), 2.28-2.17 (m, 4H), 2.04-1.89 (m, 8H), 1.80 (ddd, J=14.3, 8.4, 2.5 Hz, 1H), 1.75-1.56 (m, 4H), 1.52 (ddd, J=11.2, 9.3, 3.4 Hz, 1H), 1.14 (d, J=6.3 Hz, 3H), 1.12 (s, 3H), 1.09 (s, 3H), 0.88 (s, 9H), 0.08 (s, 3H), 0.08 (s, 3H); 125 MHz 13C NMR (CDCl3) δ 207.5, 159.5, 144.6, 144.4, 138.0, 137.3, 130.6, 129.7, 129.2, 128.6, 128.0, 127.9, 114.1, 109.0, 108.9, 104.0, 93.4, 79.4, 75.4 (×2), 75.2, 75.1, 75.0, 72.0, 70.8, 69.8, 69.6, 60.5, 55.5, 52.8, 44.4, 42.9, 41.8, 41.5, 41.2, 41.0 (×2), 40.5, 38.2, 37.7, 36.8, 30.7, 26.1, 23.1, 22.1, 18.3, 14.0, −3.8, −4.4; 125 MHz DEPT 13C NMR (CDCl3) CH3 δ 55.5, 52.8, 26.1, 23.1, 22.1, 14.0, −3.8, −4.4; CH2 δ 109.0, 108.9, 93.4, 72.0, 69.6, 60.5, 42.9, 41.8, 41.5, 41.2, 41.0 (×2), 40.5, 38.2, 37.7, 36.8, 30.6; CH δ 137.3, 129.7, 129.2, 128.6, 128.0, 127.9, 114.1, 79.4, 75.4 (×2), 75.2, 75.1, 75.0, 70.8, 69.8; CH0 δ 207.5, 159.5, 144.6, 144.4, 138.0, 130.6, 104.0, 44.4, 18.3; IR (neat) 3446, 2937, 2857, 2360, 1725, 1652, 1613, 1514, 1463, 1381, 1303, 1250, 1113, 1042, 777 cm−1; HRMS (EI+) calcd for C53H78O10Si (M-MeOH) 902.5370. found 902.5381.

Workup

  1. additionwas added a solution
  2. washvia cannula, rinsing once with DMF (300 μL)
  3. additionthe reaction mixture was diluted with 40% EtOAc/hexanes (5 mL)
  4. customquenched with water (5 mL)
  5. customThe phases were separated
  6. extractionthe aqueous phase was extracted three times with 40% EtOAc/hexanes (5 mL)
  7. dry with materialThe combined organic phases were dried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customPurification
  11. washeluting with 30% EtOAc/hexanes
  12. customcollecting 13×100 mm test tube fractions
  13. additionThe product containing fractions (6-35)
  14. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-8f6f22bd1d8d47b89bffc14cbb280f24
Source dataset
uspto-grants-2015_08
Patent number
US09096550B2

Reaction notes

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