3-(Trifluoromethyl)benzaldehyde → Methyl 10-bromo-9-fluoro-3-(hydroxy(3-(trifluoromethyl)phenyl)methyl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine-2-carboxylate

HRID 575099Notes

Reaction equation

HRID 575099 reaction equation
[Br:1][C:2]1[C:3]([F:20])=[CH:4][C:5]2[O:11][CH2:10][CH2:9][N:8]3[CH:12]=[C:13]([C:15]([O:17][CH3:18])=[O:16])[N:14]=[C:7]3[C:6]=2[CH:19]=1.[Li+].[Cl-].[F:23][C:24]([F:34])([F:33])[C:25]1[CH:26]=[C:27]([CH:30]=[CH:31][CH:32]=1)[CH:28]=[O:29]>C1COCC1>[Br:1][C:2]1[C:3]([F:20])=[CH:4][C:5]2[O:11][CH2:10][CH2:9][N:8]3[C:12]([CH:28]([OH:29])[C:27]4[CH:30]=[CH:31][CH:32]=[C:25]([C:24]([F:23])([F:33])[F:34])[CH:26]=4)=[C:13]([C:15]([O:17][CH3:18])=[O:16])[N:14]=[C:7]3[C:6]=2[CH:19]=1

Participants

5

Reactant 3

HCID 679903-(Trifluoromethyl)benzaldehydeHCID 433294Lithium ChlorideHCID 86693131Methyl 10-bromo-9-fluoro-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine-2-carboxylate

Product 1

HCID 86693130Methyl 10-bromo-9-fluoro-3-(hydroxy(3-(trifluoromethyl)phenyl)methyl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine-2-carboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

The title compound was prepared similarly according to the procedure in Example 9. Methyl 10-bromo-9-fluoro-5,6-dihydroimidazo[1,2-d][1,4]benzoxazepine-2-carboxylate (150 mg, 0.44 mmol) was dissolved in THF (1.3 mL, 3 mL/mmol) and the solution was cooled to 0° C. A solution of TMPMgCl/LiCl (1 M in toluene/THF, 1.6 equiv., 0.704 mL, 0.70 mmol) was added down the side of the vial slowly. The mixture was allowed to stir for 30 minutes. After 30 minutes, 3-(trifluoromethyl)benzaldehyde (1.0 equiv., 0.06 mL, 0.44 mmol) was added and the reaction continued to stir for 30 minutes. The reaction was quenched with saturated NH4Cl and extracted 3 times with methylene chloride. The organic layers were combined, dried with Na2SO4 and concentrated. The crude was purified by flash chromatography to afford 73 mg (32.2% yield) of a white solid.

Workup

  1. waitAfter 30 minutes
  2. stirringto stir for 30 minutes
  3. customThe reaction was quenched with saturated NH4Cl
  4. extractionextracted 3 times with methylene chloride
  5. dry with materialdried with Na2SO4
  6. concentrationconcentrated
  7. customThe crude was purified by flash chromatography

Sources & evidence

ORD record
ord-a43d16bc62a94c42b9027b91430a6ab5
Source dataset
uspto-grants-2015_05
Patent number
US09034866B2

Reaction notes

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