Acetic Anhydride → 5-(R)-(2-(S)-Acetylamino-1-(S)-hydroxy-3-phenyl-propyl)-2-(S)-(2-cyclohexyl-ethyl)-morpholine-4-carboxylic acid tert-butyl ester

HRID 20372Notes

Reaction equation

HRID 20372 reaction equation
[C:1]([O:5][C:6]([N:8]1[C@@H:13]([C@@H:14]([OH:24])[C@@H:15]([NH2:23])[CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH2:12][O:11][C@@H:10]([CH2:25][CH2:26][CH:27]2[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.[C:40](OC(=O)C)(=[O:42])[CH3:41]>O1CCCC1.ClCCl>[C:1]([O:5][C:6]([N:8]1[C@@H:13]([C@@H:14]([OH:24])[C@@H:15]([NH:23][C:40](=[O:42])[CH3:41])[CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH2:12][O:11][C@@H:10]([CH2:25][CH2:26][CH:27]2[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]2)[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 3

HCID 7918Acetic AnhydrideHCID 8471TriethylamineHCID 685618115-(R)-(2-(S)-Amino-1-(S)-hydroxy-3-phenylpropyl)-2-(S)-(2-cyclohexylethyl)-morpholine-4-carboxylic acid tert-butyl ester

Product 1

HCID 685610175-(R)-(2-(S)-Acetylamino-1-(S)-hydroxy-3-phenyl-propyl)-2-(S)-(2-cyclohexyl-ethyl)-morpholine-4-carboxylic acid tert-butyl esterYield 54.8%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

Dissolve 5-(R)-(2-(S)-amino-1-(S)-hydroxy-3-phenylpropyl)-2-(S)-(2-cyclohexylethyl)-morpholine-4-carboxylic acid tert-butyl ester (140 mg, 0.31 mmol) in dry tetrahydrofuran (3 mL). Add triethylamine (0.05 mL, 0.35 mmol) followed by acetic anhydride (0.03 mL, 0.35 mmol) and stir at room temperature for 1 hour. Dilute with dichloromethane, wash with 0.1 N hydrochloric acid/saturated aqueous sodium chloride (30 mL), dry (sodium sulfate), filter, concentrate and purify (silica gel chromatography, eluting with 40:60 to 60:40 ethyl acetate:dichloromethane) acetate/dichloromethane to give the title compound (83 mg, 54%).

Workup

  1. washwash with 0.1 N hydrochloric acid/saturated aqueous sodium chloride (30 mL)
  2. dry with materialdry (sodium sulfate)
  3. filtrationfilter
  4. concentrationconcentrate
  5. custompurify (silica gel chromatography, eluting with 40:60 to 60:40 ethyl acetate:dichloromethane) acetate/dichloromethane

Sources & evidence

ORD record
ord-723717d5cb214f459decbdbf05a3a82b
Source dataset
uspto-grants-2010_06
Patent number
US07745438B2

Reaction notes

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