o-Xylyl bromide → HCID 66741758, compound

HRID 409383Notes

Reaction equation

HRID 409383 reaction equation
[Cl:1][C:2]1[CH:29]=[CH:28][C:5]2[N:6]([CH2:19][C:20]3[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[CH:22][CH:21]=3)[C:7](=[O:18])[CH2:8][N:9]=[C:10]([C:11]3[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=3)[C:4]=2[CH:3]=1.CC(C)([O-])C.[K+].[CH3:36][C:37]1[CH:44]=[CH:43][CH:42]=[CH:41][C:38]=1[CH2:39]Br>C1COCC1>[Cl:1][C:2]1[CH:29]=[CH:28][C:5]2[N:6]([CH2:19][C:20]3[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[CH:22][CH:21]=3)[C:7](=[O:18])[CH:8]([CH2:36][C:37]3[CH:44]=[CH:43][CH:42]=[CH:41][C:38]=3[CH3:39])[N:9]=[C:10]([C:11]3[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=3)[C:4]=2[CH:3]=1

Participants

5

Reactant 3

HCID 6992o-Xylyl bromideHCID 23665647Potassium tert-butoxideHCID 66741762HCID 66741762, compound

Product 1

HCID 66741758HCID 66741758, compoundYield 39%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

7-Chloro-5-(4-fluorophenyl)-1-(4-methoxybenzyl)-1H-benzo[e][1,4]diazepin-2(3H)-one (90 mg, 0.220 mmol) was dissolved in dry THF (2 mL) and cooled to −78° C. under nitrogen. Potassium tert-butoxide (49 mg, 0.437 mmol) was added as a solid in one portion and the resulting red solution was stirred vigorously for 5 min. To this solution was added 2-methylbenzyl bromide (25 μL, 0.262 mmol) by syringe. The mixture was stirred for 1 h at −78° C., then the cold bath was removed. After another 1 h (warming to room temperature), the reaction was quenched with MeOH and diluted with ethyl acetate. The organic layer was washed twice with water and once with brine, and then dried over MgSO4. Chromatography on silica gel eluting with 100% hexanes to 30% ethyl acetate in hexanes provided 7-chloro-5-(4-fluorophenyl)-1-(4-methoxybenzyl)-3-(2-methylbenzyl)-1H-benzo[e][1,4]diazepin-2(3H)-one (44 mg, 39%). APCI MS m/z 535.2 [M+Na+], 513.3 [M+]; 1H NMR (300 MHz, CDCl3) δ 7.43-6.98 (m, 11H), 6.88 (d, J=9 Hz, 2H), 6.61 (dd, J=7 Hz, 2 Hz, 2H), 5.69 (d, J=15 Hz, 1H), 4.55 (d, J=15 Hz, 1H), 3.85 (t, J=7 Hz, 1H), 3.70 (s, 3H), 3.63 (d, J=7 Hz, 2H), 2.37 (s, 3H).

Workup

  1. stirringThe mixture was stirred for 1 h at −78° C.
  2. customthe cold bath was removed
  3. temperatureAfter another 1 h (warming to room temperature)
  4. customthe reaction was quenched with MeOH
  5. additiondiluted with ethyl acetate
  6. washThe organic layer was washed twice with water and once with brine
  7. dry with materialdried over MgSO4

Sources & evidence

ORD record
ord-85e51eec909247a5869c29ee0c53b7d4
Source dataset
uspto-grants-2014_06
Patent number
US08759340B2

Reaction notes

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