Water → methyl 4-[(1S)-1-[[(2R)-3-methyl-2-(2-phenoxyethoxy)butanoyl]amino]ethyl]benzoate

HRID 1466538Notes

Reaction equation

HRID 1466538 reaction equation
[O:1]([CH2:8][CH2:9][OH:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CC(C)([O-])C.[K+].[CH3:17][CH:18]([CH3:40])[C@@H:19](OS(C)(=O)=O)[C:20]([NH:22][C@H:23]([C:25]1[CH:34]=[CH:33][C:28]([C:29]([O:31][CH3:32])=[O:30])=[CH:27][CH:26]=1)[CH3:24])=[O:21].O>C1COCC1>[CH3:17][CH:18]([CH3:40])[C@@H:19]([O:10][CH2:9][CH2:8][O:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)[C:20]([NH:22][C@H:23]([C:25]1[CH:26]=[CH:27][C:28]([C:29]([O:31][CH3:32])=[O:30])=[CH:33][CH:34]=1)[CH3:24])=[O:21]

Participants

6

Reactant 4

HCID 962WaterHCID 31236PhenoxyethanolHCID 23665647Potassium tert-butoxideHCID 86730615methyl 4-[(1S)-1-[[(2R)-3-methyl-2-methylsulfonyloxy-butanoyl]amino]ethyl]benzoate

Product 1

HCID 86730614methyl 4-[(1S)-1-[[(2R)-3-methyl-2-(2-phenoxyethoxy)butanoyl]amino]ethyl]benzoateYield 60%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Under a nitrogen atmosphere, 2-phenoxyethanol (17.3 mL, 138 mmol) in THF (450 mL) is cooled to 5° C. using an ice water bath and treated dropwise over 5 min with a 1M solution of potassium tert-butoxide in THF (138 mL, 138 mmol). The mixture is stirred for 30 min, and methyl 4-[(1S)-1-[[(2R)-3-methyl-2-methylsulfonyloxy-butanoyl]amino]ethyl]benzoate (45 g, 126 mmol) is added in one portion. The mixture is stirred to room temperature for 1 h, and water (300 mL) is added. The layers are separated, and the aqueous layer is extracted with ethyl acetate (100 mL). The combined organic layers are washed with brine, dried over MgSO4, filtered, and concentrated. The crude material is purified using silica gel column chromatography (750 g cartridge; 20 to 60% ethyl acetate in heptane) to provide the title compound as a white solid (30 g, 60%). MS (m/z): 400.4 (M+1).

Workup

  1. stirringThe mixture is stirred to room temperature for 1 h
  2. customThe layers are separated
  3. extractionthe aqueous layer is extracted with ethyl acetate (100 mL)
  4. washThe combined organic layers are washed with brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude material is purified

Sources & evidence

ORD record
ord-cb875c031a424c439629a95a1017b009
Source dataset
uspto-grants-2015_04
Patent number
US09000043B2

Reaction notes

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