alpha-Bromo-o-chlorotoluene → HCID 59594394, compound

HRID 885010Notes

Reaction equation

HRID 885010 reaction equation
[Cl:1][C:2]1[CH:30]=[CH:29][C:5]2[N:6]([CH2:20][C:21]3[CH:26]=[CH:25][C:24]([O:27][CH3:28])=[CH:23][CH:22]=3)[C:7](=[O:19])[CH2:8][N:9]=[C:10]([C:11]3[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[CH:13][CH:12]=3)[C:4]=2[CH:3]=1.CC(C)([O-])C.[K+].[Cl:37][C:38]1[CH:45]=[CH:44][CH:43]=[CH:42][C:39]=1[CH2:40]Br>C1COCC1>[Cl:1][C:2]1[CH:30]=[CH:29][C:5]2[N:6]([CH2:20][C:21]3[CH:26]=[CH:25][C:24]([O:27][CH3:28])=[CH:23][CH:22]=3)[C:7](=[O:19])[CH:8]([CH2:40][C:39]3[CH:42]=[CH:43][CH:44]=[CH:45][C:38]=3[Cl:37])[N:9]=[C:10]([C:11]3[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[CH:13][CH:12]=3)[C:4]=2[CH:3]=1

Participants

5

Reactant 3

HCID 11905alpha-Bromo-o-chlorotolueneHCID 23665647Potassium tert-butoxideHCID 59594384HCID 59594384, compound

Product 1

HCID 59594394HCID 59594394, compoundYield 29%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

(Z)-7-Chloro-1-(4-methoxybenzyl)-5-(4-methoxyphenyl)-1H-benzo[e][1,4]diazepin-2(3H)-one (0.344 g, 0.817 mmol) was dissolved in dry THF (8 mL) and cooled to −78° C. under nitrogen. Potassium tert-butoxide (0.119 g, 1.063 mmol) was added in one portion. The reaction mixture was stirred for 5 min. turning deep red. 2-chlorobenzylbromide (0.128 mL, 0.981 mmol) was added by syringe. The mixture was stirred at −78° C. for 1.5 h then the cold bath was removed. After 1 h, the reaction was quenched with methanol and diluted with ethyl acetate. The organic layer was washed with water (2×) then brine and dried (MgSO4). Chromatography on silica gel eluting with 25-30% ethyl acetate in hexanes gave (Z)-7-chloro-3-(2-chlorobenzyl)-1-(4-methoxybenzyl)-5-(4-methoxyphenyl)-1H-benzo[e][1,4]diazepin-2(3H)-one (128 mg, 29%). 1H NMR (300 MHz, CDCl3) δ 3.6-3.8 (m, 2H), 3.7 (s, 3H), 3.8 (s, 3H), 3.9-4.0 (m, 1H), 4.55 (d, 1H), 5.7 (d, 1H), 6.6 (d, 2H), 6.8-6.9 (m, 4H), 7.1-7.4 (m, 8H), 7.6 (dd, 1H); ESI m/z.

Workup

  1. stirringThe mixture was stirred at −78° C. for 1.5 h
  2. customthe cold bath was removed
  3. waitAfter 1 h
  4. customthe reaction was quenched with methanol
  5. additiondiluted with ethyl acetate
  6. washThe organic layer was washed with water (2×)
  7. dry with materialbrine and dried (MgSO4)

Sources & evidence

ORD record
ord-b1dd232e7e9141899a8eed040755e6e2
Source dataset
uspto-grants-2012_08
Patent number
US08242109B2

Reaction notes

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