Sodium hydride → HCID 20135081, compound

HRID 580397Notes

Reaction equation

HRID 580397 reaction equation
[H-].[Na+].[CH3:3][O:4][C:5]([CH:7]1[CH:13]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[O:20][CH3:21])[CH2:12][C:11]2[CH:22]=[C:23]([C:26]([F:29])([F:28])[F:27])[CH:24]=[CH:25][C:10]=2[NH:9][C:8]1=[O:30])=[O:6].Br[CH2:32][O:33][CH3:34]>CN(C)C=O>[CH3:3][O:4][C:5]([CH:7]1[CH:13]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[O:20][CH3:21])[CH2:12][C:11]2[CH:22]=[C:23]([C:26]([F:29])([F:27])[F:28])[CH:24]=[CH:25][C:10]=2[N:9]([CH2:32][O:33][CH3:34])[C:8]1=[O:30])=[O:6]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 83093Bromomethyl methyl etherHCID 201350951,3,4,5-Tetrahydro-3-(methoxycarbonyl)-4-(methoxyphenyl)-7-(trifluoromethyl)-2H-1-benzazepin-2-one

Product 1

HCID 20135081HCID 20135081, compoundYield 76.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a suspension of sodium hydride (360 mg; 7.5 mmole; 50% oil dispersion/prewashed with dry ether several times) in dry dimethylformamide (30 ml), cooled at 0°-5° C. was added a solution of 1,3,4,5-tetrahydro-3-(methoxycarbonyl)-4-(methoxyphenyl)-7-(trifluoromethyl)-2H-1-benzazepin-2-one (1.9 g; 5 mmole) in dry dimethylformamide (15 ml) dropwise and with stirring. The mixture was stirred for an additional 20 minutes at 0°-5° C., whereupon bromomethylmethyl ether (800 μl; 10 mmole) was added dropwise, and stirring was continued at this temperature for an additional hour. Excess sodium hydride was destroyed by the addition of water, and the mixture was diluted with ether and washed with water. The aqueous layer was extracted with ether (three times) and the combined extracts were dried (magnesium sulfate) and concentrated. The crude oily residue was flash chromatographed (silica gel/5-25% ethyl acetate:hexane) to obtain 1.67 g of the title compound as an oil.

Workup

  1. temperaturecooled at 0°-5° C.
  2. additionwas added dropwise
  3. stirringstirring
  4. waitwas continued at this temperature for an additional hour
  5. customExcess sodium hydride was destroyed by the addition of water
  6. additionthe mixture was diluted with ether
  7. washwashed with water
  8. extractionThe aqueous layer was extracted with ether (three times)
  9. dry with materialthe combined extracts were dried (magnesium sulfate)
  10. concentrationconcentrated
  11. customchromatographed (silica gel/5-25% ethyl acetate:hexane)

Sources & evidence

ORD record
ord-3fba0eea40214bbda207eea22a95b2cf
Source dataset
uspto-grants-1988_06
Patent number
US04752645

Reaction notes

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