Sodium hydride → methyl 3-[5-(2-tert-butylsilyloxypropan-2-yl)-3-[4-[(2-methylquinolin-4-yl)methoxy]phenyl]-4H-1,2-oxazol-5-yl]prop-2-enoate

HRID 1245404Notes

Reaction equation

HRID 1245404 reaction equation
[CH3:1][O:2][C:3]([CH2:5]P(OC)(OC)=O)=[O:4].[H-].[Na+].[C:14]([SiH2:18][O:19][C:20]([CH3:48])([CH3:47])[C:21]1([CH:45]=O)[O:25][N:24]=[C:23]([C:26]2[CH:31]=[CH:30][C:29]([O:32][CH2:33][C:34]3[C:43]4[C:38](=[CH:39][CH:40]=[CH:41][CH:42]=4)[N:37]=[C:36]([CH3:44])[CH:35]=3)=[CH:28][CH:27]=2)[CH2:22]1)([CH3:17])([CH3:16])[CH3:15]>CN(C=O)C>[CH3:1][O:2][C:3](=[O:4])[CH:5]=[CH:45][C:21]1([C:20]([CH3:48])([CH3:47])[O:19][SiH2:18][C:14]([CH3:17])([CH3:16])[CH3:15])[O:25][N:24]=[C:23]([C:26]2[CH:31]=[CH:30][C:29]([O:32][CH2:33][C:34]3[C:43]4[C:38](=[CH:39][CH:40]=[CH:41][CH:42]=4)[N:37]=[C:36]([CH3:44])[CH:35]=3)=[CH:28][CH:27]=2)[CH2:22]1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 80029Trimethyl phosphonoacetateHCID 1317259975-(2-tert-butylsilyloxypropan-2-yl)-3-[4-[(2-methylquinolin-4-yl)methoxy]phenyl]-4H-1,2-oxazole-5-carbaldehyde

Product 1

HCID 131725998methyl 3-[5-(2-tert-butylsilyloxypropan-2-yl)-3-[4-[(2-methylquinolin-4-yl)methoxy]phenyl]-4H-1,2-oxazol-5-yl]prop-2-enoateYield 20%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Trimethyl phosphonoacetate (0.4 g, 2.2 mmol) was added to a suspension of sodium hydride (hexane washed) (0.088 g, 60% in oil, 2.2 mmol) in DMF (7 mL) under a nitrogen atmosphere at 0° C. The reaction was stirred for 0.5 h and the aldehyde from step 24c was added. The reaction was stirred for 1 h and then partitioned between ethyl acetate and water. The organic layer was washed with brine, dried over magnesium sulfate, and concentrated to give an oil. The product was purified by FCC on silica gel eluting methylene chloride:ethyl acetate (60:50) to give 3-{5-(tert-butyl-dimethyl-silanyloxymethyl)-3-[4-(2-methyl-quinolin-4-ylmethoxy)-phenyl]-4,5-dihydro-isoxazol-5-yl}-acrylic acid methyl ester (0.24 g, 20%) as an oil. MS found: (M+H)+=547.

Workup

  1. stirringThe reaction was stirred for 1 h
  2. custompartitioned between ethyl acetate and water
  3. washThe organic layer was washed with brine
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated
  6. customto give an oil
  7. customThe product was purified by FCC on silica gel
  8. washeluting methylene chloride:ethyl acetate (60:50)

Sources & evidence

ORD record
ord-48cf224a15504aa8b9995eb6079ed590
Source dataset
uspto-grants-2006_10
Patent number
US07125870B2

Reaction notes

Loading…