Hydrochloric Acid → 2-(3-Trifluoromethoxyphenyl)sulfonyl-5-methyl-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole hydrochloride

HRID 2036700Notes

Reaction equation

HRID 2036700 reaction equation
[F:1][C:2]([F:37])([F:36])[O:3][C:4]1[CH:5]=[C:6]([S:10]([C:13]2[CH:21]=[CH:20][C:19]3[N:18]([CH3:22])[C:17]4[CH2:23][CH:24]5[NH:28][CH:27]([C:16]=4[C:15]=3[C:14]=2C(OC(C)(C)C)=O)[CH2:26][CH2:25]5)(=[O:12])=[O:11])[CH:7]=[CH:8][CH:9]=1.[ClH:38]>C(OCC)C>[ClH:38].[F:37][C:2]([F:1])([F:36])[O:3][C:4]1[CH:5]=[C:6]([S:10]([C:13]2[CH:14]=[C:15]3[C:19](=[CH:20][CH:21]=2)[N:18]([CH3:22])[C:17]2[CH2:23][CH:24]4[NH:28][CH:27]([C:16]3=2)[CH2:26][CH2:25]4)(=[O:12])=[O:11])[CH:7]=[CH:8][CH:9]=1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 67085643Tert-butyl 2-(3-trifluoromethoxyphenyl)sulfonyl-5-methyl-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole-carboxylate

Product 1

HCID 529132172-(3-Trifluoromethoxyphenyl)sulfonyl-5-methyl-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole hydrochloride

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Procedure

The product of step A was subjected to Boc-deprotection with 2 M HCl in diethyl ether following the procedure of Example 28, step B. The crude material was purified by flash column chromatography (SiO2, 90:9.9:0.1 dichloromethane/methanol/ammonium hydroxide). The free base was treated with 1.25 M HCl in methanol (1 mL) and the solution concentrated in vacuo to give 2-(3-trifluoromethoxyphenyl)sulfonyl-5-methyl-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole hydrochloride (30 mg, 34%, AUC HPLC >99%) as an off-white solid: mp 193-196° C.; 1H NMR (CD3OD, 300 MHz): δ 8.31 (m, 1H), 7.91-7.99 (m, 1H), 7.79-7.85 (m, 1H), 7.71-7.78 (m, 1H), 7.58-7.70 (m, 2H), 7.48-7.57 (m, 1H), 5.26-5.34 (m, 1H), 4.50-4.60 (m, 1H), 3.72 (s, 3H), 3.49 (dd, J=17.4, J=4.2 Hz, 1H), 3.07 (d, J=17.7 Hz, 1H), 2.20-2.52 (m, 3H), 1.91-2.03 (m, 1H). ESI MS m/z 437 [M+H]+

Workup

  1. customThe crude material was purified by flash column chromatography (SiO2, 90:9.9:0.1 dichloromethane/methanol/ammonium hydroxide)
  2. additionThe free base was treated with 1.25 M HCl in methanol (1 mL)
  3. concentrationthe solution concentrated in vacuo

Sources & evidence

ORD record
ord-1f6dae88cefe458ca5661cf10e4211e5
Source dataset
uspto-grants-2013_11
Patent number
US08575186B2

Reaction notes

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