Acetic Anhydride → (2S,3S,5R)-5-[(1S,2S)-2-Acetylamino-3-(3-fluoro-5-hydroxy-phenyl)-1-hydroxypropyl]-3-methyl-2-(2,2,2-trifluoro-ethoxy)-morpholine-4-carboxylic acid tert-butyl ester

HRID 20470Notes

Reaction equation

HRID 20470 reaction equation
[C:1](OC(=O)C)(=[O:3])[CH3:2].[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]([OH:30])[CH:27]=[C:26]([F:31])[CH:25]=2)[CH2:19][O:18][C@@H:17]([O:34][CH2:35][C:36]([F:39])([F:38])[F:37])[C@@H:16]1[CH3:40])=[O:14])([CH3:11])([CH3:10])[CH3:9].C(N(C(C)C)CC)(C)C>ClCCl>[C:8]([O:12][C:13]([N:15]1[C@@H:20]([C@@H:21]([OH:33])[C@@H:22]([NH:32][C:1](=[O:3])[CH3:2])[CH2:23][C:24]2[CH:29]=[C:28]([OH:30])[CH:27]=[C:26]([F:31])[CH:25]=2)[CH2:19][O:18][C@@H:17]([O:34][CH2:35][C:36]([F:39])([F:37])[F:38])[C@@H:16]1[CH3:40])=[O:14])([CH3:11])([CH3:9])[CH3:10]

Participants

5

Reactant 3

HCID 7918Acetic AnhydrideHCID 81531DiisopropylethylamineHCID 68560206(2S,3S,5R)-5-[(1S,2S)-2-Amino-3-(3-fluoro-5-hydroxy-phenyl)-1-hydroxy-propyl]-3-methyl-2-(2,2,2-trifluoro-ethoxy)-morpholine-4-carboxylic acid tert-butyl ester

Product 1

HCID 68559574(2S,3S,5R)-5-[(1S,2S)-2-Acetylamino-3-(3-fluoro-5-hydroxy-phenyl)-1-hydroxypropyl]-3-methyl-2-(2,2,2-trifluoro-ethoxy)-morpholine-4-carboxylic acid tert-butyl esterYield 65.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Add acetic anhydride (0.142 mL, 1.51 mmol) to an ice cold solution of (2S,3S,5R)-5-[(1S,2S)-2-Amino-3-(3-fluoro-5-hydroxy-phenyl)-1-hydroxy-propyl]-3-methyl-2-(2,2,2-trifluoro-ethoxy)-morpholine-4-carboxylic acid tert-butyl ester (823 mg, 1.43 mmol) in dichloromethane (9 mL). Stir for 50 minutes and add diisopropylethylamine (0.125 mL, 0.717 mmol) and stir for 2 hours. Quench with aqueous 1N hydrochloric acid, wash with saturated aqueous sodium bicarbonate, dry with magnesium sulfate and purify on silica gel with dichloromethane/ethyl acetate mixtures to give the desired compound (493 mg). MS(ESI): m/z=525 [M+H]+.

Workup

  1. stirringstir for 2 hours
  2. customQuench with aqueous 1N hydrochloric acid
  3. washwash with saturated aqueous sodium bicarbonate
  4. dry with materialdry with magnesium sulfate
  5. custompurify on silica gel with dichloromethane/ethyl acetate

Sources & evidence

ORD record
ord-f25edbd8e161447a8fbe90f9c7cd0a52
Source dataset
uspto-grants-2010_06
Patent number
US07745438B2

Reaction notes

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