Hydrochloric Acid → (Z)-2-[4,4-difluoro-1-(4-methyl-2-phenylthiazole-5-carbonyl)-2,3,4,5-tetrahydro-1H-1-benzoazepin-5-ylidene]ethanol

HRID 1251080Notes

Reaction equation

HRID 1251080 reaction equation
[F:1][C:2]1([F:31])[CH2:3][CH2:4][N:5]([C:17]([C:19]2[S:23][C:22]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)=[N:21][C:20]=2[CH3:30])=[O:18])[C:6]2[CH:16]=[CH:15][CH:14]=[CH:13][C:7]=2/[C:8]/1=[CH:9]/[C:10](O)=[O:11].Cl.C(N=C=NCCCN(C)C)C.ON1C(=O)CCC1=O.[BH4-].[Na+].Cl>ClCCl.O1CCCC1.C(OCC)(=O)C>[F:31][C:2]1([F:1])[CH2:3][CH2:4][N:5]([C:17]([C:19]2[S:23][C:22]([C:24]3[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=3)=[N:21][C:20]=2[CH3:30])=[O:18])[C:6]2[CH:16]=[CH:15][CH:14]=[CH:13][C:7]=2/[C:8]/1=[CH:9]/[CH2:10][OH:11]

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 80170N-HydroxysuccinimideHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 4311764Sodium borohydrideHCID 70160918(Z)-2-[4,4-difluoro-1-(4-methyl-2-phenylthiazole-5-carbonyl)-2,3,4,5-tetrahydro-1H-1-benzoazepin-5-ylidene]acetic acid

Product 1

HCID 70162330(Z)-2-[4,4-difluoro-1-(4-methyl-2-phenylthiazole-5-carbonyl)-2,3,4,5-tetrahydro-1H-1-benzoazepin-5-ylidene]ethanolYield 20%

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 1.19 g of (Z)-2-[4,4-difluoro-1-(4-methyl-2-phenylthiazole-5-carbonyl)-2,3,4,5-tetrahydro-1H-1-benzoazepin-5-ylidene]acetic acid in 100 ml of dichloromethane were added 623 mg of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide monohydrochloride and 374 mg of N-hydroxysuccinimide, and the mixture was stirred at room temperature for 14 hours. The reaction solution was washed with water and dried over anhydrous magnesium sulfate. The residue obtained by evaporation of the solvent was dissolved in 40 ml of tetrahydrofuran, and 112 mg of sodium borohydride was added with ice cooling, followed by stirring at 0° C. for 24 hours. To the reaction solution were added ethyl acetate and 0.5N hydrochloric acid to undergo liquid separation, the organic layer was washed with a saturated aqueous solution of sodium bicarbonate and a saturated aqueous solution of NaCl, followed by drying over anhydrous magnesium sulfate. The residue obtained by evaporation of the solvent was purified by silica gel column chromatography (eluting with ethyl acetate-n-hexane) to give 230 mg of (Z)-2-[4,4-difluoro-1-(4-methyl-2-phenylthiazole-5-carbonyl)-2,3,4,5-tetrahydro-1H-1-benzoazepin-5-ylidene]ethanol as a colorless amorphous solid.

Workup

  1. washThe reaction solution was washed with water
  2. dry with materialdried over anhydrous magnesium sulfate
  3. customThe residue obtained by evaporation of the solvent
  4. stirringby stirring at 0° C. for 24 hours
  5. customliquid separation
  6. washthe organic layer was washed with a saturated aqueous solution of sodium bicarbonate
  7. dry with materialby drying over anhydrous magnesium sulfate
  8. customThe residue obtained by evaporation of the solvent
  9. customwas purified by silica gel column chromatography (eluting with ethyl acetate-n-hexane)

Sources & evidence

ORD record
ord-4da7cf4ebcbc4732b9eee6d35a3afb58
Source dataset
uspto-grants-2002_01
Patent number
US06340678B1

Reaction notes

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