Lithium Hydroxide → n-Tert-butoxycarbonyl-1-morpholin-4-yl-1-oxo-3-(phenylthio)propan-2-amine

HRID 2085724Notes

Reaction equation

HRID 2085724 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]([C:18]([O:20]C)=O)[CH2:10][S:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[OH-].[Li+].[NH:24]1[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1.CCN=C=NCCCN(C)C>CO.CN(C1C=CN=CC=1)C.C(OCC)(=O)C.CN(C=O)C>[C:1]([O:5][C:6]([NH:8][CH:9]([CH2:10][S:11][C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1)[C:18]([N:24]1[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1)=[O:20])=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

9

Reactant 4

HCID 3939Lithium HydroxideHCID 8083MorpholineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 18637399Methyl n-(tert-butoxycarbonyl)-s-phenylcysteinate

Product 1

HCID 22730433n-Tert-butoxycarbonyl-1-morpholin-4-yl-1-oxo-3-(phenylthio)propan-2-amine

Reagents, catalysts & solvents 4

HCID 142844-(Dimethylamino)pyridineCatalystHCID 887MethanolSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of Example 175A (600 mg, 1.92 mmol) and 2M aqueous lithium hydroxide (4 mL) in methanol (10 mL) at room temperature was stirred for 5 hours and concentrated. The concentrate was treated with morpholine (263 mg, 3 mmol), EDCI (555 mg, 2.88 mmol), DMAP (20 mg) and DMF (20 mL), stirred for 16 hours, diluted with ethyl acetate (100 mL), washed sequentially with water (50 mL), and brine (20 mL), dried (MgSO4), filtered, and concentrated. The concentrate was purified by flash column chromatography on silica gel with 50% ethyl acetate/hexanes to provide the desired product. MS (ESI(+)) m/e 367 (M+H)+.

Workup

  1. concentrationconcentrated
  2. washwashed sequentially with water (50 mL), and brine (20 mL)
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe concentrate was purified by flash column chromatography on silica gel with 50% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-efad821a118045f68de0b2518d06cad2
Source dataset
uspto-grants-2004_04
Patent number
US06720338B2

Reaction notes

Loading…