Triethylamine → Butanoic acid, 2-[[(1,1-dimethylethyl)dimethylsilyl]oxy]-4-hydroxy-, methyl ester, (S)-

HRID 1775768Notes

Reaction equation

HRID 1775768 reaction equation
[OH:1][C@H:2]1C[CH2:5][O:4][C:3]1=[O:7].C(N([CH2:13][CH3:14])CC)C.[Si:15](Cl)([C:18]([CH3:21])([CH3:20])[CH3:19])([CH3:17])[CH3:16].[Cl-].[NH4+].C[O-:26].[Na+]>CN(C1C=CN=CC=1)C.CO.ClCCl>[O:1]([C@@H:2]([CH2:13][CH2:14][OH:26])[C:3]([O:4][CH3:5])=[O:7])[Si:15]([C:18]([CH3:21])([CH3:20])[CH3:19])([CH3:17])[CH3:16]

Participants

9

Reactant 5

HCID 8471TriethylamineHCID 25517Ammonium Chloride2×HCID 28928tert-Butyldimethylsilyl chlorideHCID 3578532-Hydroxy-gamma-butyrolactone, (2S)-HCID 10942334Sodium Methoxide

Product 1

HCID 11107713Butanoic acid, 2-[[(1,1-dimethylethyl)dimethylsilyl]oxy]-4-hydroxy-, methyl ester, (S)-Yield 14.8%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

(Step 1) To (S)-3-hydroxydihydrofuran-2(3H)-one (0.5 mL, 6.41 mmol), dichloromethane (6.4 mL), triethylamine (1.34 mL, 9.62 mmol), tert-butyldimethylsilylchloride (1.06 g, 7.07 mmol), and DMAP (39 mg, 0.321 mmol) were added, and the resulting mixture was stirred at room temperature for 3 hours. To the reaction mixture, a saturated aqueous ammonium chloride solution was added, and the resulting mixture was extracted with ethyl acetate. The organic layer was dried over sodium sulfate, and the solvent was evaporated under reduced pressure. To the obtained residue, methanol (11 mL) and sodium methoxide (331 mg, 6.13 mmol) were added, and the resulting mixture was stirred at 50° C. for 2.5 hours. The reaction mixture was cooled to room temperature, and a saturated aqueous ammonium chloride solution was added thereto, and then, the resulting mixture was extracted with ethyl acetate. The organic layer was dried over sodium sulfate, and the solvent was evaporated under reduced pressure. The resulting residue was purified by silica gel column chromatography (ethyl acetate/n-hexane=0/100 to 30/70), whereby methyl (S)-2-(tert-butyldimethylsiloxy)-4-hydroxybutanoate (225 mg, 14%) was obtained.

Workup

  1. extractionthe resulting mixture was extracted with ethyl acetate
  2. dry with materialThe organic layer was dried over sodium sulfate
  3. customthe solvent was evaporated under reduced pressure
  4. stirringthe resulting mixture was stirred at 50° C. for 2.5 hours
  5. temperatureThe reaction mixture was cooled to room temperature
  6. extractionthe resulting mixture was extracted with ethyl acetate
  7. dry with materialThe organic layer was dried over sodium sulfate
  8. customthe solvent was evaporated under reduced pressure
  9. customThe resulting residue was purified by silica gel column chromatography (ethyl acetate/n-hexane=0/100 to 30/70)

Sources & evidence

ORD record
ord-e863dc89757a44acaa1705ec2e49005c
Source dataset
uspto-grants-2016_02
Patent number
US09260459B2

Reaction notes

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