Acetic Anhydride → (R)-5-[(1S,2S)-2-Acetylamino-3-(3,5-difluorophenyl)-1-hydroxypropyl]-2,2-diphenylmorpholine-4-carboxylic acid tert-butyl ester

HRID 20399Notes

Reaction equation

HRID 20399 reaction equation
[C:1]([O:5][C:6]([N:8]1[C@@H:13]([C@@H:14]([OH:26])[C@@H:15]([NH2:25])[CH2:16][C:17]2[CH:22]=[C:21]([F:23])[CH:20]=[C:19]([F:24])[CH:18]=2)[CH2:12][O:11][C:10]([C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.[C:46](OC(=O)C)(=[O:48])[CH3:47]>O1CCCC1.C(OCC)(=O)C>[C:1]([O:5][C:6]([N:8]1[C@@H:13]([C@@H:14]([OH:26])[C@@H:15]([NH:25][C:46](=[O:48])[CH3:47])[CH2:16][C:17]2[CH:22]=[C:21]([F:23])[CH:20]=[C:19]([F:24])[CH:18]=2)[CH2:12][O:11][C:10]([C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)([C:27]2[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 3

HCID 7918Acetic AnhydrideHCID 8471TriethylamineHCID 68561345(R)-5-[(1S,2S)-2-Amino-3-(3,5-difluorophenyl)-1-hydroxypropyl]-2,2-diphenylmorpholine-4-carboxylic acid tert-butyl ester

Product 1

HCID 68561953(R)-5-[(1S,2S)-2-Acetylamino-3-(3,5-difluorophenyl)-1-hydroxypropyl]-2,2-diphenylmorpholine-4-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

Dissolve (R)-5-[(1S,2S)-2-amino-3-(3,5-difluorophenyl)-1-hydroxypropyl]-2,2-diphenylmorpholine-4-carboxylic acid tert-butyl ester (0.163 g, 0.31 mmol) in tetrahydrofuran (4 mL). Add triethylamine (0.044 g, 0.44 mmol) and acetic anhydride (0.036 g, 0.35 mmol). Stir 90 minutes and dilute with ethyl acetate (50 mL). Wash with 0.1 N aqueous citric acid, water, and saturated aqueous sodium chloride. Dry (magnesium sulfate), filter and concentrate. Purify on silica gel, eluting with 10:90 to 50:50 ethyl acetate:hexanes to give the title compound.

Workup

  1. washWash with 0.1 N aqueous citric acid, water, and saturated aqueous sodium chloride
  2. dry with materialDry (magnesium sulfate)
  3. filtrationfilter
  4. concentrationconcentrate
  5. customPurify on silica gel
  6. washeluting with 10:90 to 50:50 ethyl acetate

Sources & evidence

ORD record
ord-83a81dbca46e4b418686bdd23f9a4fc5
Source dataset
uspto-grants-2010_06
Patent number
US07745438B2

Reaction notes

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