3-Bromobenzyl bromide → HCID 59594399, compound

HRID 2263691Notes

Reaction equation

HRID 2263691 reaction equation
C(=O)=O.CC(C)=O.[Cl:8][C:9]1[CH:37]=[CH:36][C:12]2[N:13]([CH2:27][C:28]3[CH:33]=[CH:32][C:31]([O:34][CH3:35])=[CH:30][CH:29]=3)[C:14](=[O:26])[CH2:15][N:16]=[C:17]([C:18]3[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[CH:20][CH:19]=3)[C:11]=2[CH:10]=1.CC([O-])(C)C.[K+].[Br:44][C:45]1[CH:46]=[C:47]([CH:50]=[CH:51][CH:52]=1)[CH2:48]Br>C1COCC1>[Br:44][C:45]1[CH:46]=[C:47]([CH:50]=[CH:51][CH:52]=1)[CH2:48][CH:15]1[C:14](=[O:26])[N:13]([CH2:27][C:28]2[CH:33]=[CH:32][C:31]([O:34][CH3:35])=[CH:30][CH:29]=2)[C:12]2[CH:36]=[CH:37][C:9]([Cl:8])=[CH:10][C:11]=2[C:17]([C:18]2[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[CH:20][CH:19]=2)=[N:16]1

Participants

6

Reactant 4

HCID 699793-Bromobenzyl bromideHCID 18522661Acetone cardiceHCID 23665647Potassium tert-butoxideHCID 59594384HCID 59594384, compound

Product 1

HCID 59594399HCID 59594399, compoundYield 84.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a stirred and cooled (dry ice/acetone bath) solution of (Z)-7-chloro-1-(4-methoxybenzyl)-5-(4-methoxyphenyl)-1H-benzo[e][1,4]diazepin-2(3H)-one (6.00 g, 14.2 mmol) in THF (80 mL) was slowly added 1 M KOtBu (21 mL, 21 mmol, 1.5 eq). The resulting deep red mixture was stirred over dry ice/acetone bath ˜10 min followed by the slow addition of a solution of 3-bromobenzyl bromide (5.10 g, 21.4 mmol, 1.5 eq) in THF (15 mL). After stirring another ˜45 min at −78° C., the reaction mixture was quenched with saturated brine and diluted with EtOAc. The organic layer was dried (Na2SO4), filtered and evaporated (rotovap, then high vacuum). Chromatography over silica gel using 10-30% EtOAc/heptane gave 7.08 g (yield of 84%) of the title product. [Note: when using benzyl chlorides as alkylating agents, tetrabutyl ammonium iodide was added along with the alkylating agent at the low temperature]. 1H NMR (300 MHz, CDCl3) δ 3.57 (d, 2H), 3.70 (s, 3H), 3.73 (t, 1H), 3.83 (s, 3H), 4.59 (d, 1H), 5.62 (d, 1H), 6.61 (d, 2H), 6.8-6.9 (m, 4H), 7.2-7.45 (m, 8H), 7.63 (fine d, 1H).

Workup

  1. stirringThe resulting deep red mixture was stirred over dry ice/acetone bath ˜10 min
  2. stirringAfter stirring another ˜45 min at −78° C.
  3. customthe reaction mixture was quenched with saturated brine
  4. additiondiluted with EtOAc
  5. dry with materialThe organic layer was dried (Na2SO4)
  6. filtrationfiltered
  7. customevaporated (rotovap

Sources & evidence

ORD record
ord-e832989760a54cc488ff0ba2275d19f1
Source dataset
uspto-grants-2010_12
Patent number
US07851465B2

Reaction notes

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