Acetic Anhydride → HCID 68561198, compound

HRID 20433Notes

Reaction equation

HRID 20433 reaction equation
[C:1]([O:5][C:6]([N:8]1[C@@H:13]([C@@H:14]([OH:26])[C@@H:15]([NH2:25])[CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=2[CH2:23][CH3:24])[CH2:12][O:11][C@@H:10]([O:27][CH2:28][C:29]([CH3:32])([CH3:31])[CH3:30])[C@@H:9]1[CH3:33])=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:34](OC(=O)C)(=[O:36])[CH3:35].C(N(CC)CC)C>ClCCl>[C:1]([O:5][C:6]([N:8]1[C@@H:13]([C@@H:14]([OH:26])[C@@H:15]([NH:25][C:34](=[O:36])[CH3:35])[CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=2[CH2:23][CH3:24])[CH2:12][O:11][C@@H:10]([O:27][CH2:28][C:29]([CH3:31])([CH3:30])[CH3:32])[C@@H:9]1[CH3:33])=[O:7])([CH3:3])([CH3:4])[CH3:2]

Participants

5

Reactant 3

HCID 7918Acetic AnhydrideHCID 8471TriethylamineHCID 68560674(2R,3S,5R)-5-[(1S,2S)-2-Amino-3-(2-ethylphenyl)-1-hydroxypropyl]-2-(2,2-dimethylpropoxy)-3-methylmorpholine-4-carboxylic acid tert-butyl ester

Product 1

HCID 68561198HCID 68561198, compoundYield 53.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Dissolve the diastereomeric mixture of amines from the previous reaction which contains (2R,3S,5R)-5-[(1S,2S)-2-amino-3-(2-ethylphenyl)-1-hydroxypropyl]-2-(2,2-dimethylpropoxy)-3-methylmorpholine-4-carboxylic acid tert-butyl ester (418 mg, 0.9 mmol) in dry dichloromethane (7 mL) under a nitrogen atmosphere and add acetic anhydride (90 μL, 0.95 mmol) and triethylamine (150 μL, 1.1 mmol). After 4 hours quench with methanol, concentrate and purify (silica gel chromatography) to give a mixture of amide diastereomers containing the title compound (243 mg). Purify the resulting mixture by HPLC, eluting with 65:35 acetonitrile:water with 8 μM hydrochloric acid, to give the title compound as a single diastereomer (47 mg, 10% overall).

Workup

  1. dissolutionDissolve
  2. customfrom the previous reaction which
  3. customAfter 4 hours quench with methanol
  4. concentrationconcentrate
  5. custompurify (silica gel chromatography)
  6. customto give

Sources & evidence

ORD record
ord-d49128d3f159495c81403c00affe8f15
Source dataset
uspto-grants-2010_06
Patent number
US07745438B2

Reaction notes

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