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

HRID 20379Notes

Reaction equation

HRID 20379 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[C@@H: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][C@@H:24]([CH2:41][OH:42])[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:32]=[C:33]([F:38])[CH:34]=[C:35]([F:37])[CH:36]=2)[CH2:26][O:25][C@@H:24]([CH2:41][OH:42])[CH2:23]1)=[O:21])([CH3:17])([CH3:18])[CH3:16]

Participants

5

Reactant 3

HCID 7918Acetic AnhydrideHCID 8471TriethylamineHCID 68562765HCID 68562765, compound

Product 1

HCID 68559754(R)-5-[2-(S)-Acetylamino-3-(3,5-difluorophenyl)-1-(S)-hydroxypropyl]-2-(R)-hydroxymethylmorpholine-4-carboxylic acid tert-butyl esterYield 68.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Add triethylamine (0.623 mL, 4.473 mmol) and acetic anhydride (0.281 mL, 2.982 mmol) to a solution of (R)-5-[2-(S)-amino-3-(3,5-difluorophenyl)-1-(S)-hydroxypropyl]-2-(R)-hydroxymethylmorpholine-4-carboxylic acid tert-butyl ester (1.20 g, 2.982 mmol) in tetrahydrofuran (30 mL). Stir at room temperature for 45 minutes, concentrate and purify (silica gel chromatography, eluting with 6:94 to 9:91 methanol:dichloromethane) to give the title compound as a white foam (0.906 g, 68.4%).

Workup

  1. concentrationconcentrate
  2. custompurify
  3. wash(silica gel chromatography, eluting with 6:94 to 9:91 methanol:dichloromethane)

Sources & evidence

ORD record
ord-94f8f4057ccc404ea2913fee5d3256b6
Source dataset
uspto-grants-2010_06
Patent number
US07745438B2

Reaction notes

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