N-Methoxy-N,2-dimethyl-1,3-oxazole-4-carboxamide → HCID 86658082, compound

HRID 577894Notes

Reaction equation

HRID 577894 reaction equation
C([Li])(CC)C.[Si:6]([O:23][CH2:24][C:25]1[C:30]([N:31]2[CH2:36][C@H:35]([CH3:37])[O:34][C@H:33]([CH3:38])[CH2:32]2)=[C:29]([F:39])[C:28]([F:40])=[CH:27][CH:26]=1)([C:19]([CH3:22])([CH3:21])[CH3:20])([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.CON(C)[C:44]([C:46]1[N:47]=[C:48]([CH3:51])[O:49][CH:50]=1)=[O:45]>C1COCC1>[Si:6]([O:23][CH2:24][C:25]1[C:30]([N:31]2[CH2:36][C@H:35]([CH3:37])[O:34][C@H:33]([CH3:38])[CH2:32]2)=[C:29]([F:39])[C:28]([F:40])=[C:27]([C:44]([C:46]2[N:47]=[C:48]([CH3:51])[O:49][CH:50]=2)=[O:45])[CH:26]=1)([C:19]([CH3:21])([CH3:22])[CH3:20])([C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1

Participants

5

Reactant 3

HCID 24828113N-Methoxy-N,2-dimethyl-1,3-oxazole-4-carboxamideHCID 67357593(2R,6S)-4-(6-((tert-butyldiphenylsilyloxy)methyl)-2,3-difluorophenyl)-2,6-dimethylmorpholine2×HCID 178418400CID 53628100

Product 1

HCID 86658082HCID 86658082, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

sec-Butyl lithium (1.4 M in cyclohexane, 3.2 eq) was added to a stirred solution of (2R,6S)-4-[6-({[tert-butyl(diphenyl)silyl]oxy}methyl)-2,3-difluorophenyl]-2,6-dimethylmorpholine (Intermediate 3, 1.0 g, 2.02 mmol) in anhydrous THF (10 mL) at −78° C., and the mixture was stirred for 2 h. N-methoxy-N,2-dimethyl-1,3-oxazole-4-carboxamide (1.0 g, 6.46 mmol) in THF (5 mL) was added dropwise and stirring was continued for an additional 1 h. The reaction mixture was quenched with saturated ammonium chloride solution and extracted with ethyl acetate. The organic layer was washed with brine and dried over anhydrous sodium sulphate. The solvent was removed under vacuum and the residue was purified by silica gel chromatography using ethylacetate-pet. ether gradient to obtain product. Yield: 600 mg, (50%)

Workup

  1. stirringstirring
  2. waitwas continued for an additional 1 h
  3. customThe reaction mixture was quenched with saturated ammonium chloride solution
  4. extractionextracted with ethyl acetate
  5. washThe organic layer was washed with brine
  6. dry with materialdried over anhydrous sodium sulphate
  7. customThe solvent was removed under vacuum
  8. customthe residue was purified by silica gel chromatography
  9. customto obtain product

Sources & evidence

ORD record
ord-2a20a5a8e0de4f559f39c2313c7ef1e8
Source dataset
uspto-grants-2015_05
Patent number
US09040528B2

Reaction notes

Loading…