Dimethylformamide → N-{(S)-2-(3-Cyclopropylmethoxy-phenyl)-1-[(1S,5S,6R,8aR)-6-(2,2-dimethyl-propoxy)-5-methyl-3-oxo-tetrahydro-oxazolo[4,3-c][1,4]oxazin-1-yl]-ethyl}-acetamide

HRID 20468Notes

Reaction equation

HRID 20468 reaction equation
C([O:8][C:9]([N:11]1[C@@H:16]([C@@H:17](O)[C@@H:18]([NH:27][C:28](=[O:30])[CH3:29])[CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[C:22]([OH:26])[CH:21]=2)[CH2:15][O:14][C@@H:13]([O:32][CH2:33][C:34]([CH3:37])([CH3:36])[CH3:35])[C@@H:12]1[CH3:38])=[O:10])C1C=CC=CC=1.[CH:39]1([CH2:42]Br)[CH2:41][CH2:40]1.C(=O)([O-])[O-].[Cs+].[Cs+].CN(C)C=O>C(OCC)(=O)C>[CH:39]1([CH2:42][O:26][C:22]2[CH:21]=[C:20]([CH2:19][C@H:18]([NH:27][C:28](=[O:30])[CH3:29])[C@H:17]3[C@H:16]4[CH2:15][O:14][C@@H:13]([O:32][CH2:33][C:34]([CH3:36])([CH3:37])[CH3:35])[C@H:12]([CH3:38])[N:11]4[C:9](=[O:8])[O:10]3)[CH:25]=[CH:24][CH:23]=2)[CH2:41][CH2:40]1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 10796Cesium carbonateHCID 81503BromomethylcyclopropaneHCID 68558723HCID 68558723, compound

Product 1

HCID 68557941N-{(S)-2-(3-Cyclopropylmethoxy-phenyl)-1-[(1S,5S,6R,8aR)-6-(2,2-dimethyl-propoxy)-5-methyl-3-oxo-tetrahydro-oxazolo[4,3-c][1,4]oxazin-1-yl]-ethyl}-acetamideYield 85.9%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

Heat a mixture of (2R,3S,5R)-5-[(1S,2S)-2-Acetylamino-1-hydroxy-3-(3-hydroxy-phenyl)-propyl]-2-(2,2-dimethyl-propoxy)-3-methyl-morpholine-4-carboxylic acid benzyl ester (69 mg, 0.13 mmol), cyclopropylmethyl bromide (0.019 ml, 0.195 mmol), cesium carbonate (127 mg, 0.39 mmol) and N,N-dimethylformamide (2 mL) to 60° C. for 18 hours. Cool and dilute with ethyl acetate and wash with saturated sodium chloride, dry with magnesium sulfate and purify on silica gel with dichloromethane/ethyl acetate mixtures to give the desired compound (53 mg). MS(ESI): m/z=475 [M+H]+.

Workup

  1. temperatureHeat
  2. temperatureCool
  3. washwash with saturated sodium chloride
  4. dry with materialdry with magnesium sulfate
  5. custompurify on silica gel with dichloromethane/ethyl acetate

Sources & evidence

ORD record
ord-07780f64b7034387ba33e00e182ac59e
Source dataset
uspto-grants-2010_06
Patent number
US07745438B2

Reaction notes

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