Sodium Hydroxide → 9,10-Dichloro-6-[2-(4-fluorophenoxy)ethyl]-1,2,3,4,5,6-hexahydroazepino[4,5-b]indole hydrochloride

HRID 2307003Notes

Reaction equation

HRID 2307003 reaction equation
[Cl:1][C:2]1[CH:10]=[CH:9][C:8]2[N:7]([CH2:11][CH2:12][O:13][C:14]3[CH:19]=[CH:18][C:17]([F:20])=[CH:16][CH:15]=3)[C:6]3[CH2:21][CH2:22][N:23](C(OC(C)(C)C)=O)[CH2:24][CH2:25][C:5]=3[C:4]=2[C:3]=1[Cl:33].[OH-].[Na+]>C(Cl)Cl.C(O)(C(F)(F)F)=O>[ClH:1].[Cl:1][C:2]1[CH:10]=[CH:9][C:8]2[N:7]([CH2:11][CH2:12][O:13][C:14]3[CH:15]=[CH:16][C:17]([F:20])=[CH:18][CH:19]=3)[C:6]3[CH2:21][CH2:22][NH:23][CH2:24][CH2:25][C:5]=3[C:4]=2[C:3]=1[Cl:33]

Participants

5

Reactant 2

HCID 14798Sodium HydroxideHCID 22396705tert-Butyl 9,10-dichloro-6-[2-(4-fluorophenoxy)ethyl]-1,4,5,6-tetrahydroazepino[4,5-b]indole-3(2H)-carboxylate

Product 1

HCID 223968029,10-Dichloro-6-[2-(4-fluorophenoxy)ethyl]-1,2,3,4,5,6-hexahydroazepino[4,5-b]indole hydrochlorideYield 78.3%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 6422Trifluoroacetic acidSolvent

Procedure

To a solution of tert-butyl 9,10-dichloro-6-[2-(4-fluorophenoxy)ethyl]-1,4,5,6-tetrahydroazepino[4,5-b]indole-3(2H)-carboxylate (0.20 g, 0.41 mmol) in CH2Cl2 (6.0 mL), TFA (0.63 mL, 8.1 minol) was added while stirring at rt. After 30 min, the reaction was made basic with 10% aqueous NaOH, then extracted with CH2Cl2 (3×15 mL). The combined organic layers were washed with brine, dried over Na2SO4, decanted, and concentrated to 0.17 g of a crude solid. After the hydrochloride salt was prepared, it was further purified by a recrystallization from MeOH/EtOAc to give 69 mg (40%) of a white solid: mp 214.0-216.0; 1H NMR (300 MHz, DMSO) δ 7.58 (d, J=8.7 Hz, 1H), 7.31 (d, J=9.0 Hz, 1H), 7.09 (m, 2H), 6.84 (m, 2H), 4.63 (m, 2H), 4.15 (t, J=4.9 Hz, 2H), 3.53 (m, 2H), 13C NMR (400 MHz, DMSO) δ 157.0, 154.7, 153.5, 153.5, 139.5, 134.4, 123.2, 122.0, 121.2, 120.7, 115.2, 115.0, 114.8, 114.7, 110.0, 109.9, 66.6, 44.5, 42.9, 41.6, 21.6, 20.5; IR (diffuse reflectance) 2965, 2838, 2823, 2794, 2770, 2745, 2714, 2697, 2651, 1506, 1442, 1249, 1222, 1206, 831 cm−1; MS (ES+) m/z 393 (M+H+), 364, 238, 221, 175, 79, 74, 66, 64, 62, 61. Anal. Calcd for C20H19Cl2FN2O.HCl: C, 55.90; H, 4.69; N, 6.52, found: C, 55.65; H, 4.72; N, 6.49.

Workup

  1. extractionextracted with CH2Cl2 (3×15 mL)
  2. washThe combined organic layers were washed with brine
  3. dry with materialdried over Na2SO4
  4. customdecanted
  5. concentrationconcentrated to 0.17 g of a crude solid
  6. customAfter the hydrochloride salt was prepared
  7. customit was further purified by a recrystallization from MeOH/EtOAc

Sources & evidence

ORD record
ord-be6f205044114a55a648213362d2c916
Source dataset
uspto-grants-2004_12
Patent number
US06828314B2

Reaction notes

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