2-Bromobenzyl bromide → HCID 58386897, compound

HRID 885004Notes

Reaction equation

HRID 885004 reaction equation
[Cl:1][C:2]1[C:3]2[CH:22]=[C:21]([Cl:23])[CH:20]=[CH:19][C:4]=2[N:5]([CH2:10][C:11]2[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[CH:13][CH:12]=2)[C:6](=[O:9])[CH2:7]N=1.[CH3:24]C(C)([O-])C.[K+].[Br:30][C:31]1[CH:38]=[CH:37][CH:36]=[CH:35][C:32]=1[CH2:33]Br>C1COCC1>[Br:30][C:31]1[CH:38]=[CH:37][CH:36]=[CH:35][C:32]=1[CH2:33][CH:7]1[C:6](=[O:9])[N:5]([CH2:10][C:11]2[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[CH:13][CH:12]=2)[C:4]2[CH:19]=[CH:20][C:21]([Cl:23])=[CH:22][C:3]=2[C:2]([Cl:1])=[CH:24]1

Participants

5

Reactant 3

HCID 769652-Bromobenzyl bromideHCID 23665647Potassium tert-butoxideHCID 59594371HCID 59594371, compound

Product 1

HCID 58386897HCID 58386897, compoundYield 74%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a solution of (E)-5,7-dichloro-1-(4-methoxybenzyl)-1H-benzo[e][1,4]diazepin-2(3H)-one (0.45 g, 1.28 mmol) in anhydrous THF (20 mL), was added at −78° C. under a N2 atmosphere, a solution of potassium tert-butoxide (1 M in THF, 1.54 mL, 1.54 mmol). After completion of the addition the reaction mixture was stirred for ½ h at −78° C. and a solution of 2-bromobenzylbromide (0.386 mL, 1.54 mmol) in THF (5 mL) was added at −78° C. drop-wise over 15 minutes. The reaction mixture was stirred at −78° C. for 2 more hours and then the temperature was raised to room temperature. The reaction mixture was left at room temperature overnight under a N2 atmosphere. The reaction mixture was quenched with saturated NH4Cl (50 mL) and extracted with EtOAc (3×50 mL). The combined extracts were washed with brine (100 mL), dried (MgSO4) and evaporated in vacuo. The crude material was purified by flash column chromatography (eluted with 20% EtOAc in Hexane) to give (E)-3-(2-bromobenzyl)-5,7-dichloro-1-(4-methoxybenzyl)-1H-benzo[b]azepin-2(3H)-one (0.49 g, 74%) as a pale solid. 1H NMR (400 MHz, DMSO-d6) δ 3.65 (s, 3H), 4.06-4.10 (m, 2H), 4.86 (d, 1H), 5.39 (d, 1H), 4.79 (d, 2H), 6.92 (d, 2H), 7.12-7.39 (m, 3H), 7.54-7.56 (m, 1H), 7.67-7.82 (m, 3H). MS m/z 519.20 [M+1].

Workup

  1. additionAfter completion of the addition the reaction mixture
  2. stirringThe reaction mixture was stirred at −78° C. for 2 more hours
  3. temperaturethe temperature was raised to room temperature
  4. waitThe reaction mixture was left at room temperature overnight under a N2 atmosphere
  5. customThe reaction mixture was quenched with saturated NH4Cl (50 mL)
  6. extractionextracted with EtOAc (3×50 mL)
  7. washThe combined extracts were washed with brine (100 mL)
  8. dry with materialdried (MgSO4)
  9. customevaporated in vacuo
  10. customThe crude material was purified by flash column chromatography (eluted with 20% EtOAc in Hexane)

Sources & evidence

ORD record
ord-71e2f41f3fdd4a7aa180ac068ad95f44
Source dataset
uspto-grants-2012_08
Patent number
US08242109B2

Reaction notes

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