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

HRID 20377Notes

Reaction equation

HRID 20377 reaction equation
C(N(CC)CC)C.[C:8](OC(=O)C)(=[O:10])[CH3:9].[C:15]([O:19][C:20]([N:22]1[CH:27]([C@@H:28]([OH:40])[C@@H:29]([NH2:39])[CH2:30][C:31]2[CH:36]=[C:35]([F:37])[CH:34]=[C:33]([F:38])[CH:32]=2)[CH2:26][O:25][CH:24]([CH2:41][O:42][C:43]2[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=2)[CH2:23]1)=[O:21])([CH3:18])([CH3:17])[CH3:16]>O1CCCC1>[C:15]([O:19][C:20]([N:22]1[C@@H:27]([C@@H:28]([OH:40])[C@@H:29]([NH:39][C:8](=[O:10])[CH3:9])[CH2:30][C:31]2[CH:36]=[C:35]([F:37])[CH:34]=[C:33]([F:38])[CH:32]=2)[CH2:26][O:25][C@@H:24]([CH2:41][O:42][C:43]2[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=2)[CH2:23]1)=[O:21])([CH3:18])([CH3:16])[CH3:17]

Participants

5

Reactant 3

HCID 7918Acetic AnhydrideHCID 8471TriethylamineHCID 68561136HCID 68561136, compound

Product 1

HCID 68561384(2R,5R)-5-[(1S,2S)-2-Acetylamino-3-(3,5-difluorophenyl)-1-hydroxypropyl]-2-phenoxymethylmorpholine-4-carboxylic acid tert-butyl esterYield 45.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Add triethylamine (0.009 mL, 0.066 mmol) and acetic anhydride (0.004 mL, 0.044 mmol) to a solution of (2R,5R)-(5-[(1S,2S)-2-amino-3-(3,5-difluorophenyl)-1-hydroxypropyl]-2-phenoxymethyl-morpholine-4-carboxylic acid tert-butyl ester (0.021 g, 0.044 mmol) in tetrahydrofuran (0.44 mL) and stir at room temperature for 1 hour. Concentrate and purify (silica gel chromatography, eluting with 50:50 to 60:40 ethyl acetate:hexanes) to give the title compound as a white foam (0.010 g, 45.5%).

Workup

  1. concentrationConcentrate
  2. custompurify
  3. wash(silica gel chromatography, eluting with 50:50 to 60:40 ethyl acetate:hexanes)

Sources & evidence

ORD record
ord-7f1419f772d54353bc9b273be95ca889
Source dataset
uspto-grants-2010_06
Patent number
US07745438B2

Reaction notes

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