1-(Bromomethyl)-4-(trifluoromethyl)benzene → (Z)-7-Chloro-5-(4-(4-methoxybenzyloxy)phenyl)-1-methyl-3-(4-(trifluoromethyl)benzyl)-1H-benzo[e][1,4]diazepin-2(3H)-one

HRID 885018Notes

Reaction equation

HRID 885018 reaction equation
[Cl:1][C:2]1[CH:30]=[CH:29][C:5]2[N:6]([CH3:28])[C:7](=[O:27])[CH2:8][N:9]=[C:10]([C:11]3[CH:16]=[CH:15][C:14]([O:17][CH2:18][C:19]4[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][CH:20]=4)=[CH:13][CH:12]=3)[C:4]=2[CH:3]=1.CC(C)([O-])C.[K+].[F:37][C:38]([F:48])([F:47])[C:39]1[CH:46]=[CH:45][C:42]([CH2:43]Br)=[CH:41][CH:40]=1>O1CCCC1>[Cl:1][C:2]1[CH:30]=[CH:29][C:5]2[N:6]([CH3:28])[C:7](=[O:27])[CH:8]([CH2:43][C:42]3[CH:41]=[CH:40][C:39]([C:38]([F:37])([F:47])[F:48])=[CH:46][CH:45]=3)[N:9]=[C:10]([C:11]3[CH:16]=[CH:15][C:14]([O:17][CH2:18][C:19]4[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][CH:20]=4)=[CH:13][CH:12]=3)[C:4]=2[CH:3]=1

Participants

5

Reactant 3

HCID 1230621-(Bromomethyl)-4-(trifluoromethyl)benzeneHCID 23665647Potassium tert-butoxideHCID 59594389(Z)-7-Chloro-5-(4-(4-methoxybenzyloxy)phenyl)-1-methyl-1H-benzo[e][1,4]diazepin-2(3H)-one

Product 1

HCID 59594382(Z)-7-Chloro-5-(4-(4-methoxybenzyloxy)phenyl)-1-methyl-3-(4-(trifluoromethyl)benzyl)-1H-benzo[e][1,4]diazepin-2(3H)-oneYield 49%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

(Z)-7-Chloro-5-(4-(4-methoxybenzyloxy)phenyl)-1-methyl-1H-benzo[e][1,4]diazepin-2(3H)-one (75 mg, 0.18 mmol) was dissolved in tetrahydrofuran (4 mL), and the solution was cooled to −78° C. under a nitrogen atmosphere. A 1 M solution of potassium tert-butoxide in tetrahydrofuran (267 μL, 0.267 mmol) was added dropwise, and the solution was stirred for 10 minutes. 4-(trifluoromethyl)benzyl bromide (64 mg, 0.267 mmol, solution in 1 mL tetrahydrofuran) was then added dropwise, and the cooling bath was then removed. The reaction was stirred at room temperature for 2 hours, and it was then quenched with water, and the mixture was portioned between water and ethyl acetate. The aqueous portion was extracted into ethyl acetate again, and the combined organic extracts were dried over sodium sulfate, and then concentrated, and purified by chromatography (gradient; 9:1 hexanes:ethyl acetate to 6:4 hexanes:ethyl acetate, then isocratic) yielding the product as a clear residue (50 mg, 49%).

Workup

  1. customthe cooling bath was then removed
  2. stirringThe reaction was stirred at room temperature for 2 hours
  3. customit was then quenched with water
  4. extractionThe aqueous portion was extracted into ethyl acetate again
  5. dry with materialthe combined organic extracts were dried over sodium sulfate
  6. concentrationconcentrated
  7. custompurified by chromatography (gradient

Sources & evidence

ORD record
ord-6daae6fdffaf479a88f8e3f0b17affee
Source dataset
uspto-grants-2012_08
Patent number
US08242109B2

Reaction notes

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