Butyl bromide → 5-(R)-[2-(S)-Acetylamino-3-(3-butoxyphenyl)-1-(S)-hydroxypropyl]-2-(R)-(2,2-dimethylpropoxy)-3-(S)-methylmorpholine-4-carboxylic acid tert-butyl ester

HRID 20353

Reaction equation

HRID 20353 reaction equation
Br[CH2:2][CH2:3][CH2:4][CH3:5].[C:6]([O:10][C:11]([N:13]1[CH:18]([C@@H:19]([OH:33])[C@@H:20]([NH:29][C:30](=[O:32])[CH3:31])[CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[C:24]([OH:28])[CH:23]=2)[CH2:17][O:16][C@@H:15]([O:34][CH2:35][C:36]([CH3:39])([CH3:38])[CH3:37])[C@@H:14]1[CH3:40])=[O:12])([CH3:9])([CH3:8])[CH3:7].C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C)C=O.C(OCC)(=O)C>[C:6]([O:10][C:11]([N:13]1[C@@H:18]([C@@H:19]([OH:33])[C@@H:20]([NH:29][C:30](=[O:32])[CH3:31])[CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[C:24]([O:28][CH2:2][CH2:3][CH2:4][CH3:5])[CH:23]=2)[CH2:17][O:16][C@@H:15]([O:34][CH2:35][C:36]([CH3:39])([CH3:38])[CH3:37])[C@@H:14]1[CH3:40])=[O:12])([CH3:8])([CH3:9])[CH3:7]

Participants

6

Reactant 3

HCID 8002Butyl bromideHCID 10796Cesium carbonateHCID 685636245-[2-(S)-Acetylamino-1-(S)-hydroxy-3-(3-hydroxyphenyl)-propyl]-2-(R)-(2,2-dimethylpropoxy)-3-(S)-methylmorpholine-4-carboxylic acid tert-butyl ester

Product 1

HCID 589722415-(R)-[2-(S)-Acetylamino-3-(3-butoxyphenyl)-1-(S)-hydroxypropyl]-2-(R)-(2,2-dimethylpropoxy)-3-(S)-methylmorpholine-4-carboxylic acid tert-butyl esterYield 102.5%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

Add 1-bromobutane (6 μL, 55.6 μmol) to a solution of 5-[2-(S)-acetylamino-1-(S)-hydroxy-3-(3-hydroxyphenyl)-propyl]-2-(R)-(2,2-dimethylpropoxy)-3-(S)-methylmorpholine-4-carboxylic acid tert-butyl ester (25 mg, 50.5 μmol) and cesium carbonate (33 mg, 1.01 mmol) in N,N-dimethylformamide (250 μL). Heat to 60° C. for 3 hours. Dilute with ethyl acetate, wash with water, dry (magnesium sulfate), filter, concentrate and purify (silica gel chromatography, eluting with 20:80 to 85:15 ethyl acetate:dichloromethane) to give the title compound (28.5 mg, 80%).

Workup

  1. washwash with water
  2. dry with materialdry (magnesium sulfate)
  3. filtrationfilter
  4. concentrationconcentrate
  5. custompurify
  6. wash(silica gel chromatography, eluting with 20:80 to 85:15 ethyl acetate:dichloromethane)

Sources & evidence

ORD record
ord-09d161281e8047b8a1ed6073750586a1
Source dataset
uspto-grants-2010_06
Patent number
US07745438B2

Linked notes

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