Diisopropylethylamine → HCID 131733245, compound

HRID 509216Notes

Reaction equation

HRID 509216 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]/[CH:26]2[CH2:31][C:30](=[CH2:32])[CH2:29][CH:28]([CH2:33][CH:34]3[CH2:39][C@@H:38]([OH:40])[CH2:37][CH: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:46]([C:59]([CH3:62])([CH3:61])[CH3:60])([C:53]4[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=4)[C:47]4[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=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.C(N(C(C)C)CC)(C)C.[Si:93](OS(C(F)(F)F)(=O)=O)([C:96]([CH3:99])([CH3:98])[CH3:97])([CH3:95])[CH3:94]>C(Cl)Cl>[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]([CH3:23])(/[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@@H:38]([O:40][Si:93]([C:96]([CH3:99])([CH3:98])[CH3:97])([CH3:95])[CH3:94])[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:46]([C:59]([CH3:62])([CH3:61])[CH3:60])([C:53]4[CH:54]=[CH:55][CH:56]=[CH:57][CH:58]=4)[C:47]4[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=4)[O:35]3)[O:27]2)[CH3:73])([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

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 123564tert-Butyldimethylsilyl trifluoromethanesulphonateHCID 131733246HCID 131733246, compound

Product 1

HCID 131733245HCID 131733245, compoundYield 98%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of alcohol 19 (83.8 mg, 0.0712 mmol, 1.0 equiv) in CH2Cl2 (7.1 mL, 0.001M) in a 25 mL rb flask at 0° C. was added diisopropylethylamine (45.8 mg, 0.427 mmol, 6.0 equiv) and TBSOTf (47.0 mg, 0.178 mmol, 2.5 equiv) via syringe. The solution was stirred at 0° C. for 40 min, then quenched by the addition of 1.0 mL of methanol. Stirring was continued for another 10 min, and then saturated aqueous NaHCO3 solution (5 mL) was added. The aqueous phase was separated and extracted with CH2Cl2 (3×10 mL). The organic phases were combined, dried over Na2SO4 and concentrated under reduced pressure. Purification was accomplished by flash chromatography on a 4×10 cm column, eluting with 10% EtOAc/hexanes, collecting 18×150 mm test tube fractions. The product containing fractions (6-13) were combined and concentrated under reduced pressure to give the product 7 (89.3 mg, 98% yield) as a colorless oil. Rf=0.73 (20% EtOAc/Hexanes); [α]D20=+8.1 (c=0.40, CHCl3); 500 MHz 1H NMR (CDCl3) δ 7.70-7.66 (m, 4H), 7.44-7.35 (m, 11H), 7.20 (d, J=8.8 Hz, 2H), 6.86 (d, J=8.3 Hz, 2H), 6.02 (d, J=5.6 Hz, 1H), 5.47 (dd, J=16.1, 6.3 Hz, 1H), 4.78 (dd, J=10.3, 6.8 Hz, 2H), 4.65 (s, 1H), 4.63 (s, 2H), 4.56 (s, 1H), 4.46 (d, J=10.7 Hz, 1H), 4.38 (d, J=10.7 Hz, 1H), 4.14-4.04 (m, 2H), 3.95-3.88 (m, 1H), 3.85-3.71 (m, 8H), 3.60-3.50 (m, 2H), 3.50-3.44 (m, 1H), 3.29 (s, 3H), 2.43 (dd, J=8.3, 5.9 Hz, 2H), 2.29 (d, J=13.2 Hz, 1H), 2.17 (d, J=13.2 Hz, 1H), 2.04-1.90 (m, 6H), 1.86-1.72 (m, 5H), 1.68-1.48 (m, 5H), 1.16 (d, J=6.3 Hz, 3H), 1.12 (s, 3H), 1.09 (s, 3H), 1.06 (s, 9H), 0.89 (s, 9H), 0.88 (s, 9H), 0.09 (s, 3H), 0.08 (s, 3H), 0.07 (s, 3H), 0.06 (s, 3H); 125 MHz 13C NMR (CDCl3) δ 207.4, 159.3, 144.4, 138.1, 137.1, 135.8, 135.8, 134.1, 134.0, 131.3, 129.8, 129.8, 129.6, 129.4, 128.6, 128.0, 127.9, 127.9, 114.0, 109.0, 104.1, 93.4, 79.2, 75.3, 75.1, 72.9, 72.2, 72.0, 72.0, 70.8, 69.9, 69.6, 69.1, 60.6, 55.5, 52.8, 44.4, 42.8, 42.5, 42.5, 42.1, 41.2, 40.4, 38.2, 38.0, 37.7, 30.7, 27.2, 26.1, 23.3, 21.9, 19.4, 18.3, 18.3, 14.0, −3.9, −4.2, −4.3, −4.4; 125 MHz DEPT 13C NMR (CDCl3) CH3 δ 55.5, 52.8, 27.2, 26.1, 23.3, 21.9, 14.0, −3.9, −4.2, −4.3, −4.4; CH2 δ 109.0, 93.4, 72.2, 69.6, 60.6, 42.8, 42.5, 42.5, 42.1, 41.2, 40.4, 38.2, 38.0, 37.7, 30.7; CH δ 137.1, 135.8, 135.8, 129.8, 129.8, 129.6, 129.4, 128.6, 128.0, 127.9, 127.9, 114.0, 79.2, 75.3, 75.1, 72.9, 72.0, 72.0, 70.8, 69.9, 69.1, C δ 207.4, 159.3, 144.4, 138.1, 134.1, 134.0, 131.3, 104.1, 44.4, 19.4, 18.3, 18.3; IR (neat) 2930, 2856, 1728, 1513, 1465, 1382, 1250, 1110, 835, 775, 738, 703, 536 cm−1; HRMS (ESI/APCI) calcd for C75H114O12NaSi3 (M+Na) 1313.7516. found 1313.7560.

Workup

  1. customquenched by the addition of 1.0 mL of methanol
  2. stirringStirring
  3. waitwas continued for another 10 min
  4. additionsaturated aqueous NaHCO3 solution (5 mL) was added
  5. customThe aqueous phase was separated
  6. extractionextracted with CH2Cl2 (3×10 mL)
  7. dry with materialdried over Na2SO4
  8. concentrationconcentrated under reduced pressure
  9. customPurification
  10. washeluting with 10% EtOAc/hexanes
  11. customcollecting 18×150 mm test tube fractions
  12. additionThe product containing fractions (6-13)
  13. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-2fcf4234eea94318a1ff0018b2da5157
Source dataset
uspto-grants-2015_08
Patent number
US09096550B2

Reaction notes

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