Water → (Z)-7-chloro-3-(2-chlorobenzyl)-5-(4-hydroxyphenyl)-1-methyl-1H-benzo[e][1,4]diazepin-2(3H)-one

HRID 885014Notes

Reaction equation

HRID 885014 reaction equation
[Cl:1][C:2]1[CH:30]=[CH:29][C:5]2[N:6]([CH3:28])[C:7](=[O:27])[CH:8]([CH2:19][C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=3[Cl:26])[N:9]=[C:10]([C:11]3[CH:16]=[CH:15][C:14]([O:17]C)=[CH:13][CH:12]=3)[C:4]=2[CH:3]=1.B(Br)(Br)Br.O>C(Cl)Cl.[Cl-].[Na+].O>[Cl:1][C:2]1[CH:30]=[CH:29][C:5]2[N:6]([CH3:28])[C:7](=[O:27])[CH:8]([CH2:19][C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=3[Cl:26])[N:9]=[C:10]([C:11]3[CH:12]=[CH:13][C:14]([OH:17])=[CH:15][CH:16]=3)[C:4]=2[CH:3]=1

Participants

6

Reactant 3

HCID 962WaterHCID 25134Boron tribromide2×HCID 59594376HCID 59594376, compound

Product 1

HCID 135869723(Z)-7-chloro-3-(2-chlorobenzyl)-5-(4-hydroxyphenyl)-1-methyl-1H-benzo[e][1,4]diazepin-2(3H)-oneYield 8.1%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
-78 °C

Procedure

(Z)-7-chloro-3-(2-chlorobenzyl)-5-(4-methoxyphenyl)-1-methyl-1H-benzo[e][1,4]diazepin-2(3H)-one (230 mg, 0.524 mmol) was dissolved in methylene chloride (5 mL) and cooled to −78° C. under nitrogen. Boron tribromide (54 μL 0.576 mmol) was added dropwise. The mixture turned orange. It was kept at −78° C. for 2 h then allowed to warm to RT. Tlc indicated no reaction after 6 hr. An additional equivalent of boron tribromide was added. The mixture was left stirring overnight at RT. Carefully added water (2 mL) then brine (2 mL). The aqueous layer was extracted twice with methylene chloride. The combined organic layers were dried over magnesium sulfate then filtered and the solvent evaporated. The residue was chromatographed on silica gel eluting with 30-50% ethyl acetate in hexanes to give (Z)-7-chloro-3-(2-chlorobenzyl)-5-(4-hydroxyphenyl)-1-methyl-1H-benzo[e][1,4]diazepin-2(3H)-one as a yellow solid (18 mg). 1H NMR (300 MHz, CDCl3) δ 3.4 (s, 3H), 3.6-3.8 (m, 2H), 3.8-3.9 (m, 1H), 6.8 (d, 2H), 7.1-7.6 (m, 9H); ESI m/z measured 425.0828 [M+H+], calculated 425.0824.

Workup

  1. temperatureto warm to RT
  2. customno reaction after 6 hr
  3. waitThe mixture was left
  4. extractionThe aqueous layer was extracted twice with methylene chloride
  5. dry with materialThe combined organic layers were dried over magnesium sulfate
  6. filtrationthen filtered
  7. customthe solvent evaporated
  8. customThe residue was chromatographed on silica gel eluting with 30-50% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-7b4805385fd24cf7aa853f43de54e959
Source dataset
uspto-grants-2012_08
Patent number
US08242109B2

Reaction notes

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