Ammonium Hydroxide → (5aR*,10bS*)-10-(2-Fluorophenyl)-1,2,3,4,5,5a,6,10b-octahydroazepino[4,5-b]indole

HRID 2307053Notes

Reaction equation

HRID 2307053 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[C:9]2[C:10]3[CH2:21][CH2:20][NH:19][CH2:18][CH2:17][C:11]=3[NH:12][C:13]=2[CH:14]=[CH:15][CH:16]=1.CC(C)=O.C(Cl)(Cl)Cl.[NH4+].[OH-]>C1COCC1>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[C:9]2[C@@H:10]3[CH2:21][CH2:20][NH:19][CH2:18][CH2:17][C@H:11]3[NH:12][C:13]=2[CH:14]=[CH:15][CH:16]=1

Participants

5

Reactant 3

HCID 14923Ammonium HydroxideHCID 15930782Chloroform acetoneHCID 2239670010-(2-Fluorophenyl)-1,2,3,4,5,6-hexahydroazepino[4,5-b]indole

Product 1

HCID 59075500(5aR*,10bS*)-10-(2-Fluorophenyl)-1,2,3,4,5,5a,6,10b-octahydroazepino[4,5-b]indole

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 10-(2-fluorophenyl)-1,2,3,4,5,6-hexahydroazepino[4,5-b]indole (0.49 g, 1.74 mmol) in THF (6 mL) was added dropwise to 1.5 M borane-THF complex (6 mL, 9 mmol) and stirred at room temperature for 1.25 hours. The excess borane was quenched with H2O and the mixture was added to TFA at 0° C. After 0.3 hours the reaction was diluted with H2O and concentrated in vacuo. The residue was diluted with H2O, made basic with 15% NaOH and extracted three times with CH2Cl2. The extracts were dried over MgSO4 and concentrated in vacuo to give a white solid which was passed through a column of silica gel with 1:19 acetone/CHCl3 with 1% NH4OH to give 0.25 g (51%) of a light brown solid as the title compound: 1H NMR (400 MHz, CDCl3) δ 7.38-7.33 (m, 2 H), 7.21-7.10 (m, 3 H), 6.69 (d, J=7.7 Hz, 2 H), 3.89 (dt, J=11.0 Hz, 3.5 Hz, 1 H), 3.60-3.53 (m, 1 H), 3.18-3.12 (m, 1 H), 2.94-2.88 (m, 1 H), 2.83 (m, 1 H), 2.74-2.72 (m, 1 H), 2.21-2.16 (m, 1 H), 1.97-1.87 (m, 1 H), 1.67 (m, 1 H), 1.26 (m, 1 H); MS m/z 283.2 (M++H).

Workup

  1. customThe excess borane was quenched with H2O
  2. additionthe mixture was added to TFA at 0° C
  3. additionAfter 0.3 hours the reaction was diluted with H2O
  4. concentrationconcentrated in vacuo
  5. additionThe residue was diluted with H2O
  6. extractionextracted three times with CH2Cl2
  7. dry with materialThe extracts were dried over MgSO4
  8. concentrationconcentrated in vacuo
  9. customto give a white solid which

Sources & evidence

ORD record
ord-161f0b1e28df46dc9b2c3dcd7d6e9165
Source dataset
uspto-grants-2004_12
Patent number
US06828314B2

Reaction notes

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