Hydrochloric Acid → (S)-2-(tert-butyldiphenylsilyloxy)-4-(methylthio)butanoic acid

HRID 1098164Notes

Reaction equation

HRID 1098164 reaction equation
[CH3:1][S-:2].[Na+].[Si:4]([O:21][C@H:22]1[CH2:26][CH2:25][O:24][C:23]1=[O:27])([C:17]([CH3:20])([CH3:19])[CH3:18])([C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1.Cl>CN(C=O)C.C(OCC)(=O)C>[Si:4]([O:21][C@@H:22]([CH2:26][CH2:25][S:2][CH3:1])[C:23]([OH:24])=[O:27])([C:17]([CH3:20])([CH3:19])[CH3:18])([C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 4378561Sodium methanethiolateHCID 11739330(S)-3-(tert-butyldiphenylsilyloxy)dihydrofuran-2(3H)-one

Product 1

HCID 57504643(S)-2-(tert-butyldiphenylsilyloxy)-4-(methylthio)butanoic acidYield 16.98%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

Sodium thiomethoxide (0.187 g, 2.67 mmol) was added to (S)-3-(tert-butyldiphenylsilyloxy)dihydrofuran-2(3H)-one (CAS no. 220351-82-6: Klar, U.; Schwede, W.; Skuballa, W.; Buchmann, B.; Schirner, M. Ger. Offen. 1999 DE 19735575 A1) (0.826 g, 2.43 mmol) in DMF (2 mL) at 0° C. The resulting solution was stirred at room temperature for 16 hours. The reaction mixture was neutralised with 2M HCl and diluted with ethyl acetate. The organic layer was extracted with water (3×100 mL), the organic layer was dried (MgSO4) and evaporated to afford (S)-2-(tert-butyldiphenylsilyloxy)-4-(methylthio)butanoic acid (0.160 g, 16.98%) which was used without further purification. A solution of trimethylsilyldiazomethane (2M solution in ether, 0.412 ml, 0.82 mmol) was added dropwise to a stirred solution of methyl alcohol (0.167 ml, 4.12 mmol) and (S)-2-(tert-butyldiphenylsilyloxy)-4-(methylthio)butanoic acid (0.160 g, 0.41 mmol) in toluene (0.174 ml) over a period of 2 minutes. The resulting solution was stirred at ambient temperature for 2 hours. The reaction mixture was quenched with acetic acid (0.071 ml, 1.24 mmol) and stirred at ambient temperature for 10 minutes. The reaction mixture was evaporated. The residue was purified by flash silica chromatography, eluting with 0 to 50% ethyl acetate in isohexane to afford the product (0.120 g, 72.4%). 1H NMR (400 MHz, CDCl3) δ 1.09 (9H, s), 1.94-2.05 (5H, m), 2.48-2.60 (2H, m), 3.47 (3H, s), 4.33-4.36 (1H, m), 7.34-7.45 (6H, m), 7.62-7.67 (4H, m); m/z (ES+) (M-Ph)-=325; HPLC tR=3.63 min

Workup

  1. customat 0° C
  2. extractionThe organic layer was extracted with water (3×100 mL)
  3. dry with materialthe organic layer was dried (MgSO4)
  4. customevaporated

Sources & evidence

ORD record
ord-8a9400ef673c400eaef9050e5b85a927
Source dataset
uspto-grants-2012_03
Patent number
US08143263B2

Reaction notes

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