Hydrogen Bromide → HCID 24955430, compound

HRID 1095560Notes

Reaction equation

HRID 1095560 reaction equation
[CH3:1][N:2]([CH3:30])[C:3]1([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[CH2:8][CH2:7][C:6]([C:9]2[NH:10][C:11]3[C:16]([C:17]=2[CH3:18])=[CH:15][C:14]([O:19][C:20]([F:23])([F:22])[F:21])=[CH:13][CH:12]=3)=[CH:5][CH2:4]1.Br.[Sn]>>[CH3:30][N:2]([CH3:1])[C:3]1([C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=2)[CH2:8][CH2:7][CH:6]([C:9]2[NH:10][C:11]3[C:16]([C:17]=2[CH3:18])=[CH:15][C:14]([O:19][C:20]([F:23])([F:21])[F:22])=[CH:13][CH:12]=3)[CH2:5][CH2:4]1

Participants

4

Reactant 3

HCID 260Hydrogen BromideHCID 5352426Tin atomHCID 57475160HCID 57475160, compound

Product 1

HCID 24955430HCID 24955430, compound

Procedure

(±)-N,N-Dimethyl-N-[4-(3-methyl-5-trifluoromethoxy-1H-indol-2-yl)-1-phenylcyclohex-3-enyl]amine (350 mg, 0.84 mmol) was stirred with HBr/glacial acetic acid (33% HBr, 18 ml) until it had dissolved completely. Tin powder (0.98 g, 8.4 mmol) was then added to the mixture in portions in the course of 30 min. When the addition had ended, the reaction mixture was stirred for a further 1.5 h, and for working up it was then concentrated to dryness on rotary evaporator. The residue which remained was rendered basic by addition of 5 N NaOH (40 ml). The solution obtained was extracted with methylene chloride (4×30 ml). The combined organic phases were dried with Na2SO4 and then concentrated. The residue (410 mg) was separated by column chromatography [silica gel 60 (30 g); ethyl acetate/cyclohexane (1:1; 500 ml); ethyl acetate/methanol (2:1, (450 ml)]. N,N-dimethyl-4-(3-methyl-5-(trifluoromethoxy)-1H-indol-2-yl)-1-phenylcyclohexanamine (less polar diastereoisomer) was obtained in a yield of 132 mg (38%) as a colourless solid with a melting point of 78-84° C. The more polar diastereoisomer was obtained in a yield of 151 mg (43%) as a colourless solid with a melting point of 219-221° C.

Workup

  1. dissolutionhad dissolved completely
  2. additionWhen the addition
  3. concentrationwas then concentrated to dryness on rotary evaporator
  4. additionThe residue which remained was rendered basic by addition of 5 N NaOH (40 ml)
  5. customThe solution obtained
  6. extractionwas extracted with methylene chloride (4×30 ml)
  7. dry with materialThe combined organic phases were dried with Na2SO4
  8. concentrationconcentrated
  9. customThe residue (410 mg) was separated by column chromatography [silica gel 60 (30 g)

Sources & evidence

ORD record
ord-d854e12e918e48c1a38eca5ccbe8234e
Source dataset
uspto-grants-2012_03
Patent number
US08138187B2

Reaction notes

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