Monobasic potassium phosphate → (R)-4-((2S,6R)-6-(((2S,6R)-6-((E)-3-((2S,6S)-6-((2R,3R)-3-(benzyloxymethoxy)-2-(tert-butyldimethylsilyloxy)butyl)-2-methoxy-3-oxo-tetrahydro-2H-pyran-2-yl)-3-methylbut-1-enyl)-4-methylene-tetrahydro-2H-pyran-2-yl)methyl)-4-methylene-tetrahydro-2H-pyran-2-yl)-3-(4-methoxybenzyloxy)butanoic acid

HRID 509212Notes

Reaction equation

HRID 509212 reaction equation
[CH2:1]([O:8][CH2:9][O:10][C@H:11]([CH3:66])[C@H:12]([O:58][Si:59]([C:62]([CH3:65])([CH3:64])[CH3:63])([CH3:61])[CH3:60])[CH2:13][C@H:14]1[O:19][C@:18]([C:22]([CH3:56])([CH3:55])/[CH:23]=[CH:24]/[C@@H:25]2[O:30][C@H:29]([CH2:31][C@@H:32]3[O:37][C@H:36]([CH2:38][C@@H:39]([O:43][CH2:44][C:45]4[CH:50]=[CH:49][C:48]([O:51][CH3:52])=[CH:47][CH:46]=4)[CH2:40][CH:41]=[O:42])[CH2:35][C:34](=[CH2:53])[CH2:33]3)[CH2:28][C:27](=[CH2:54])[CH2:26]2)([O:20][CH3:21])[C:17](=[O:57])[CH2:16][CH2:15]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH:67]P([O-])(O)=O.[K+].[O-]Cl=O.[Na+]>CC(=CC)C.CC(O)(C)C>[CH2:1]([O:8][CH2:9][O:10][C@H:11]([CH3:66])[C@H:12]([O:58][Si:59]([C:62]([CH3:65])([CH3:64])[CH3:63])([CH3:61])[CH3:60])[CH2:13][C@H:14]1[O:19][C@:18]([C:22]([CH3:56])([CH3:55])/[CH:23]=[CH:24]/[C@@H:25]2[O:30][C@H:29]([CH2:31][C@@H:32]3[O:37][C@H:36]([CH2:38][C@@H:39]([O:43][CH2:44][C:45]4[CH:46]=[CH:47][C:48]([O:51][CH3:52])=[CH:49][CH:50]=4)[CH2:40][C:41]([OH:67])=[O:42])[CH2:35][C:34](=[CH2:53])[CH2:33]3)[CH2:28][C:27](=[CH2:54])[CH2:26]2)([O:20][CH3:21])[C:17](=[O:57])[CH2:16][CH2:15]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 516951Monobasic potassium phosphateHCID 23668197Sodium ChloriteHCID 131733239(R)-4-((2S,6R)-6-(((2S,6R)-6-((E)-3-((2S,6S)-6-((2R,3R)-3-(benzyloxymethoxy)-2-(tert-butyldimethylsilyloxy)butyl)-2-methoxy-3-oxo-tetrahydro-2H-pyran-2-yl)-3-methylbut-1-enyl)-4-methylene-tetrahydro-2H-pyran-2-yl)methyl)-4-methylene-tetrahydro-2H-pyran-2-yl)-3-(4-methoxybenzyloxyl)butanal

Product 1

HCID 131733240(R)-4-((2S,6R)-6-(((2S,6R)-6-((E)-3-((2S,6S)-6-((2R,3R)-3-(benzyloxymethoxy)-2-(tert-butyldimethylsilyloxy)butyl)-2-methoxy-3-oxo-tetrahydro-2H-pyran-2-yl)-3-methylbut-1-enyl)-4-methylene-tetrahydro-2H-pyran-2-yl)methyl)-4-methylene-tetrahydro-2H-pyran-2-yl)-3-(4-methoxybenzyloxy)butanoic acidYield 99%

Reagents, catalysts & solvents 2

HCID 6386tert-ButanolSolventHCID 105532-Methyl-2-buteneSolvent

Conditions

Temperature
-10 °C

Procedure

To a stirring solution of aldehyde 23 (26 mg, 0.028 mmol, 1.0 equiv) in 2-methyl-2-butene (400 μL) and tBuOH (400 μL), in a 10 mL rb flask at rt, was added a 1.25 M aqueous solution of KH2PO4 (134 μL). The mixture was cooled to −10° C., and NaClO2 (80%, 16 mg, 0.140 mmol, 5.0 equiv) was added in one portion. The reaction mixture stirred vigorously at −10° C. for 1.5 h, and was then quenched with aqueous pH 4 buffer solution (1 mL). The phases were separated, and the aqueous phase was extracted three times with Et2O (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 2×13 cm silica gel column, eluting with 3% MeOH/CH2Cl2, collecting 13×50 mm test tube fractions. The product containing fractions (7-10) were combined and concentrated under reduced pressure to provide pure carboxylic acid 8 (26 mg, 99%) as a clear viscous oil: Rf=0.10 (30% EtOAc/hexanes); [α]D20=+6.7 (c=0.780, CHCl3); 500 MHz 1H NMR (CDCl3) δ 7.38-7.28 (m, 5H), 7.25 (d, J=8.8 Hz, 2H), 6.88 (d, J=8.8 Hz, 2H), 6.06 (d, J=16.1 Hz, 1H), 5.47 (dd, J=16.1, 6.3 Hz, 1H), 4.80 (s, 2H), 4.73 (m, 2H), 4.67 (s, 1H), 4.65-4.62 (m, 2H), 4.61 (s, 1H), 4.57 (d, J=10.6 Hz, 1H), 4.47 (d, J=10.7 Hz, 1H), 4.14-4.05 (m, 3H), 3.86-3.75 (m, 2H), 3.80 (s, 3H), 3.56-3.41 (m, 3H), 3.30 (s, 3H), 2.66 (dd, J=15.1, 5.4 Hz, 1H), 2.58 (dd, J=15.6, 5.9 Hz, 1H), 2.47-2.43 (m, 2H), 2.28 (m, 4H), 2.05-1.90 (m, 8H), 1.83-1.76 (m, 1H), 1.75-1.65 (m, 1H), 1.59 (ddd, J=14.3, 6.4, 6.4 Hz, 1H), 1.52 (ddd, J=13.5, 9.4, 3.5 Hz, 1H), 1.16 (d, J=6.8 Hz, 3H), 1.14 (s, 3H), 0.91 (s, 3H), 0.88 (s, 9H), 0.08 (s, 6H); 125 MHz 13C NMR (CDCl3) δ 159.6, 144.4, 144.3, 137.9, 135.5, 130.2, 129.7, 129.1, 128.6, 128.1, 127.9, 114.1, 109.1, 104.0, 93.2, 79.5, 75.2, 75.1, 75.0, 72.9, 70.7, 69.7, 69.5, 55.5, 52.8, 44.3, 42.9, 41.9, 41.2, 40.9, 40.6, 40.0, 38.2, 37.6, 30.7, 26.1, 22.9, 22.3, 18.3, 14.0, −3.9, −4.4; HRMS (EI+) calcd for C53H76O11Si (M-MeOH) 916.5162. found 916.5107.

Workup

  1. customwas then quenched with aqueous pH 4 buffer solution (1 mL)
  2. customThe phases were separated
  3. extractionthe aqueous phase was extracted three times with Et2O (5 mL)
  4. dry with materialThe combined organic phases were dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customPurification
  8. washeluting with 3% MeOH/CH2Cl2
  9. customcollecting 13×50 mm test tube fractions
  10. additionThe product containing fractions (7-10)
  11. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-dd0f9d3370a3439caf0ecd98f8d46823
Source dataset
uspto-grants-2015_08
Patent number
US09096550B2

Reaction notes

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