Acetic Anhydride → HCID 68558742, compound

HRID 20357Notes

Reaction equation

HRID 20357 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]([F:30])[CH:27]=[C:26]([F:31])[CH:25]=2)[CH2:19][O:18][C@@H:17]([CH2:34][CH2:35][CH:36]([CH3:38])[CH3:37])[CH2:16]1)=[O:14])([CH3:11])([CH3:10])[CH3:9].C(N(CC)CC)C>O1CCCC1>[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:25]=[C:26]([F:31])[CH:27]=[C:28]([F:30])[CH:29]=2)[CH2:19][O:18][C@@H:17]([CH2:34][CH2:35][CH:36]([CH3:38])[CH3:37])[CH2:16]1)=[O:14])([CH3:11])([CH3:10])[CH3:9]

Participants

5

Reactant 3

HCID 7918Acetic AnhydrideHCID 8471TriethylamineHCID 68558729HCID 68558729, compound

Product 1

HCID 68558742HCID 68558742, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Add acetic anhydride (25 μL, 0.264 mmol) to a solution of 5-(R)-[2-(S)-amino-3-(3,5-difluorophenyl)-1-(S)-hydroxypropyl]-2-(S)-(3-methylbutyl)-morpholine-4-carboxylic acid tert-butyl ester (107 mg, 0.240 mmol) and triethylamine (37 μL, 0.267 mmol) in tetrahydrofuran (5 mL) and stir at room temperature for 18 hours. Concentrate and purify (silica gel chromatography, eluting with 80:20 ethyl acetate:dichloromethane), to separate the two title compounds 5-(R)-[2-(S)-acetylamino-3-(3,5-difluorophenyl)-1-(S)-hydroxypropyl]-2-(S)-(3-methylbutyl)-morpholine-4-carboxylic acid tert-butyl ester (0.141 g, 59%) and 5-(S)-[2-(R)-acetylamino-3-(3,5-difluorophenyl)-1-(R)-hydroxypropyl]-2-(S)-(3-methylbutyl)-morpholine-4-carboxylic acid tert-butyl ester (25.1 mg, 22%).

Workup

  1. concentrationConcentrate
  2. custompurify
  3. wash(silica gel chromatography, eluting with 80:20 ethyl acetate:dichloromethane)
  4. customto separate the two title compounds 5-(R)-[2-(S)-acetylamino-3-(3,5-difluorophenyl)-1-(S)-hydroxypropyl]-2-(S)-(3-methylbutyl)-morpholine-4-carboxylic acid tert-butyl ester (0.141 g, 59%) and 5-(S)-[2-(R)-acetylamino-3-(3,5-difluorophenyl)-1-(R)-hydroxypropyl]-2-(S)-(3-methylbutyl)-morpholine-4-carboxylic acid tert-butyl ester (25.1 mg, 22%)

Sources & evidence

ORD record
ord-f3eef5f3e0f7400da16188952f6f7c3e
Source dataset
uspto-grants-2010_06
Patent number
US07745438B2

Reaction notes

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