Methanol → 4-(S)-Acetylthio-5-t-butyldiphenylsilyloxypentanoic acid, methyl ester

HRID 653977Notes

Reaction equation

HRID 653977 reaction equation
[C:1]([OH:4])(=[S:3])[CH3:2].[OH-].C([N+](CCCC)(CCCC)CCCC)CCC.CO.[Si:25]([O:42][CH2:43][C@H:44](I)[CH2:45][CH2:46][C:47]([O:49][CH3:50])=[O:48])([C:38]([CH3:41])([CH3:40])[CH3:39])([C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1>C1(C)C=CC=CC=1>[C:1]([S:3][C@H:44]([CH2:43][O:42][Si:25]([C:38]([CH3:41])([CH3:40])[CH3:39])([C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)[C:32]1[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=1)[CH2:45][CH2:46][C:47]([O:49][CH3:50])=[O:48])(=[O:4])[CH3:2]

Participants

6

Reactant 4

HCID 887Methanol2×HCID 2723671Tetrabutylammonium HydroxideHCID 151260955-t-Butyldiphenylsilyloxy-4-(R)-iodopentanoic acid, methyl esterHCID 178418634HCID 178418634, compound2×

Product 1

HCID 151260964-(S)-Acetylthio-5-t-butyldiphenylsilyloxypentanoic acid, methyl ester

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Procedure

Thioacetic acid (1 mL, 13.2 mmol) was added to 20 mL of toluene under a nitrogen atmosphere. A 1 M solution of tetrabutylammonium hydroxide in methanol (11 mL, 11 mmol) with a washing of 1 mL methanol was added to the thioacetic acid solution. The methanol was removed azeotropically with toluene and residual salt redissolved in 30 mL toluene. The salt solution with a washing of 20 mL toluene was added to a solution of 8 (4.75 g, 9.6 mmol) in 50 mL toluene and stirred under nitrogen for 18 hours. After removal of solvent and precipitated salts, the crude product was purified by flash chromatography with 6:1 hexane/ethyl acetate. Yield 3.47 g (81%) of a viscous oil [α]D25 -16.0° (C=0.7, CDCl3); FAB MS 445 (M+H)+, 387 (M-t-butyl)+ ; 1H NMR (CDCl3) δ 7.65 (m, 4, ArH), 7.4 (m, 6, ArH), 3.8 (m, 1, H-4), 3.7 (s, 3, OCH3), 3.7 (m, 2, CH2), 2.35 (m, 2, CH2), 2.3 (s, 3, acetyl CH3), 2.2 (m, 1, H-2), 1.9 (m, 1, H-2), 1.05 (s, 9, t-butyl).

Workup

  1. customThe methanol was removed azeotropically with toluene and residual salt
  2. dissolutionredissolved in 30 mL toluene
  3. washThe salt solution with a washing of 20 mL toluene
  4. customAfter removal of solvent
  5. customprecipitated salts
  6. customthe crude product was purified by flash chromatography with 6:1 hexane/ethyl acetate

Sources & evidence

ORD record
ord-e57d325b455b47e38fb9dbcb01676e9c
Source dataset
uspto-grants-1992_07
Patent number
US05128458

Reaction notes

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