Methanol → HCID 18740896, compound

HRID 1935632Notes

Reaction equation

HRID 1935632 reaction equation
C(OC([NH:11][C:12]1[CH:21]=[CH:20][C:15]2[S:16][CH:17]([CH3:19])[CH2:18][C:14]=2[CH:13]=1)=O)C1C=CC=CC=1.CO.CC(C)([O-])C.[Li+].[C:30]([O:33][C@H:34]([CH2:40]Cl)[CH2:35][NH:36][C:37](=[O:39])[CH3:38])(=[O:32])C.[Cl-].[NH4+]>CN(C)C=O.CS(C)=O>[CH3:19][CH:17]1[CH2:18][C:14]2[CH:13]=[C:12]([N:11]3[CH2:40][C@@H:34]([CH2:35][NH:36][C:37](=[O:39])[CH3:38])[O:33][C:30]3=[O:32])[CH:21]=[CH:20][C:15]=2[S:16]1

Participants

8

Reactant 5

HCID 887MethanolHCID 25517Ammonium ChlorideHCID 7357675(2S)-1-Acetamido-3-chloropropan-2-yl acetateHCID 22464076HCID 22464076, compoundHCID 236647642-Propanol, 2-methyl-, lithium salt (1:1)

Product 1

HCID 18740896HCID 18740896, compound

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
5 °C

Procedure

To a 15° C. suspension of 5-{[(benzyloxy)carbonyl]amino}-2-methyl-2,3-dihydrobenzo[b]thiophene (1.5 g, 5 mmol) in dimethylformamide (3 mL) is added methanol (406 μL, 10 mmol) and then 1M lithium-t-butoxide in hexanes (15 mL, 15 mmol) dropwise over 2 h. The mixture is cooled to 5° C. and (1S)-2-(acetylamino)-1-(chloromethyl)ethyl acetate (1.94 g, 10 mmol) is added in one portion. Stirring is continued overnight at room temperature when saturated aqueous ammonium chloride (50 mL) is added and then extracted with dichloromethane, dried, and flash chromatographed on silica gel eluting with 5% methanol in dichloromethane to give 1.20 (78%) of a mixture of the title compounds. The title compounds are resolved on a Chiralpak AD column eluting with ethanol to give the 2-(−)-isomer ([α]25D=−102 (c 0.49, DMSO). Anal. Calcd for C15H18N2O3S: C, 58.80; H, 5.92; N, 9.14. Found: C, 59.03; H, 6.03; N, 8.99) and the 2-(+)-isomer ([α]25D=55 (c 0.58, DMSO). Anal. Calcd for C15H18N2O3S: C, 58.80; H, 5.92; N, 9.14. Found: C, 59.12; H, 6.09; N, 8.78.)

Workup

  1. extractionextracted with dichloromethane
  2. customdried
  3. customflash chromatographed on silica gel eluting with 5% methanol in dichloromethane
  4. customto give
  5. washeluting with ethanol
  6. customto give the 2-(−)-isomer ([α]25D=−102 (c 0.49, DMSO). Anal. Calcd for C15H18N2O3S: C, 58.80; H, 5.92; N, 9.14. Found: C, 59.03; H, 6.03; N, 8.99)

Sources & evidence

ORD record
ord-9ef8d57853604c808096008794568bd2
Source dataset
uspto-grants-2002_05
Patent number
US06387896B1

Reaction notes

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