Acetic Anhydride → (2R,5R)-5-[(1S,2S)-2-Acetylamino-3-(3-chloro-5-fluorophenyl)-1-hydroxypropyl]-2-(2,2-dimethylpropoxy)-morpholine-4-carboxylic acid tert-butyl ester

HRID 20363Notes

Reaction equation

HRID 20363 reaction equation
C(N(CC)CC)C.[C:8]([O:12][C:13]([N:15]1[C@@H:20]([C@@H:21]([OH:33])[C@@H:22]([NH2:32])[CH2:23][C:24]2[CH:29]=[C:28]([F:30])[CH:27]=[C:26]([Cl:31])[CH:25]=2)[CH2:19][O:18][C@@H:17]([O:34][CH2:35][C:36]([CH3:39])([CH3:38])[CH3:37])[CH2:16]1)=[O:14])([CH3:11])([CH3:10])[CH3:9].[C:40](OC(=O)C)(=[O:42])[CH3:41]>O1CCCC1.ClCCl>[C:8]([O:12][C:13]([N:15]1[C@@H:20]([C@@H:21]([OH:33])[C@@H:22]([NH:32][C:40](=[O:42])[CH3:41])[CH2:23][C:24]2[CH:29]=[C:28]([F:30])[CH:27]=[C:26]([Cl:31])[CH:25]=2)[CH2:19][O:18][C@@H:17]([O:34][CH2:35][C:36]([CH3:39])([CH3:38])[CH3:37])[CH2:16]1)=[O:14])([CH3:10])([CH3:9])[CH3:11]

Participants

6

Reactant 3

HCID 7918Acetic AnhydrideHCID 8471TriethylamineHCID 68561142(2R,5R)-5-[(1S,2S)-2-Amino-3-(3-chloro-5-fluorophenyl)-1-hydroxypropyl]-2-(2,2-dimethylpropoxy)-morpholine-4-carboxylic acid tert-butyl ester

Product 1

HCID 68560377(2R,5R)-5-[(1S,2S)-2-Acetylamino-3-(3-chloro-5-fluorophenyl)-1-hydroxypropyl]-2-(2,2-dimethylpropoxy)-morpholine-4-carboxylic acid tert-butyl esterYield 45.5%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

Add triethylamine (138 μL, 0.99 mmol) to a solution of (2R,5R)-5-[(1S,2S)-2-amino-3-(3-chloro-5-fluorophenyl)-1-hydroxypropyl]-2-(2,2-dimethylpropoxy)-morpholine-4-carboxylic acid tert-butyl ester (0.428 g, 0.901 mmol) in tetrahydrofuran (5 mL) followed by acetic anhydride (91 μL, 0.991 mmol). Stir at room temperature for 30 minutes, dilute with dichloromethane, wash with 0.1 N hydrochloric acid (30 mL), saturated aqueous sodium chloride (30 mL), dry (sodium sulfate), filter and purify (silica gel chromatography, eluting with 2:98 to 10:90 methanol:dichloromethane) to give the title compound as a white foam (0.212 g, 45%).

Workup

  1. washwash with 0.1 N hydrochloric acid (30 mL), saturated aqueous sodium chloride (30 mL)
  2. dry with materialdry (sodium sulfate)
  3. filtrationfilter
  4. custompurify
  5. wash(silica gel chromatography, eluting with 2:98 to 10:90 methanol:dichloromethane)

Sources & evidence

ORD record
ord-27f93aa80efa489dbe290ee599eb253f
Source dataset
uspto-grants-2010_06
Patent number
US07745438B2

Reaction notes

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