Hydrochloric Acid → 2-Phenylsulfonyl-4,5-dimethyl-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole hydrochloride

HRID 2036732Notes

Reaction equation

HRID 2036732 reaction equation
[C:1]1([S:7]([C:10]2[CH:18]=[C:17]([CH3:19])[C:16]3[N:15]([CH3:20])[C:14]4[CH2:21][CH:22]5[NH:26][CH:25]([C:13]=4[C:12]=3[C:11]=2C(OC(C)(C)C)=O)[CH2:24][CH2:23]5)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[ClH:34]>C(Cl)(Cl)Cl.C(OCC)C>[ClH:34].[C:1]1([S:7]([C:10]2[CH:11]=[C:12]3[C:16](=[C:17]([CH3:19])[CH:18]=2)[N:15]([CH3:20])[C:14]2[CH2:21][CH:22]4[NH:26][CH:25]([C:13]3=2)[CH2:24][CH2:23]4)(=[O:8])=[O:9])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 67085505Tert-butyl 2-phenylsulfonyl-4,5-dimethyl-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole-carboxylate

Product 1

HCID 670854622-Phenylsulfonyl-4,5-dimethyl-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole hydrochloride

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6212ChloroformSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of the product of step D (104 mg, 0.22 mmol) in chloroform (1 mL) was added 2 M HCl in diethyl ether solution (5 mL). The reaction was stirred at 0° C. for 1 h then allowed to warm to ambient temperature overnight. The mixture was concentrated in vacuo, made basic with sat. sodium bicarbonate solution and extracted with chloroform. The organic extract was dried over anhydrous sodium sulfate, concentrated in vacuo and the resulting residue purified by flash column chromatography (SiO2, 90:9.9:0.1 dichloromethane/methanol/ammonium hydroxide). The free-base was treated directly with 1.25 M HCl in methanol (2 mL) and the resulting solution concentrated in vacuo to give 2-phenylsulfonyl-4,5-dimethyl-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole hydrochloride (65 mg, 72%, AUC HPLC 98.7%) as a white solid: mp 244-248° C.; 1H NMR (CD3OD, 300 MHz): δ 8.08 (d, J=1.5 Hz, 1H), 7.90-7.98 (m, 2H), 7.49-7.63 (m, 3H), 7.38-7.43 (m, 1H), 5.26 (d, J=4.8 Hz, 1H), 4.49-4.58 (m, 1H), 3.94 (s, 3H), 3.44 (dd, J=17.1 Hz, J=4.5 Hz, 1H), 3.02 (d, J=17.4 Hz, 1H), 2.99 (s, 3H), 2.19-2.52 (m, 3H), 1.91-2.20 (m, 1H); APCI MS m/z 367 [M+H]+.

Workup

  1. temperatureto warm to ambient temperature overnight
  2. concentrationThe mixture was concentrated in vacuo
  3. extractionextracted with chloroform
  4. extractionThe organic extract
  5. dry with materialwas dried over anhydrous sodium sulfate
  6. concentrationconcentrated in vacuo
  7. customthe resulting residue purified by flash column chromatography (SiO2, 90:9.9:0.1 dichloromethane/methanol/ammonium hydroxide)
  8. additionThe free-base was treated directly with 1.25 M HCl in methanol (2 mL)
  9. concentrationthe resulting solution concentrated in vacuo

Sources & evidence

ORD record
ord-f9835996efdb45599318b12aa0064092
Source dataset
uspto-grants-2013_11
Patent number
US08575186B2

Reaction notes

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