Trifluoroacetic acid → 6-Chloro-8-(3-trifluoromethylphenylsulfonyl)-1,2,3,4-tetrahydrobenzofuro[3,2-c]pyridine hydrochloride

HRID 2179339Notes

Reaction equation

HRID 2179339 reaction equation
[Cl:1][C:2]1[C:7]2[O:8][C:9]3[CH2:14][CH2:13][N:12](C(OC(C)(C)C)=O)[CH2:11][C:10]=3[C:6]=2[CH:5]=[C:4]([S:22]([C:25]2[CH:30]=[CH:29][CH:28]=[C:27]([C:31]([F:34])([F:33])[F:32])[CH:26]=2)(=[O:24])=[O:23])[CH:3]=1.FC(F)(F)C(O)=O>ClCCl>[ClH:1].[Cl:1][C:2]1[C:7]2[O:8][C:9]3[CH2:14][CH2:13][NH:12][CH2:11][C:10]=3[C:6]=2[CH:5]=[C:4]([S:22]([C:25]2[CH:30]=[CH:29][CH:28]=[C:27]([C:31]([F:33])([F:32])[F:34])[CH:26]=2)(=[O:23])=[O:24])[CH:3]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 68109217tert-butyl 6-chloro-8-(3-trifluoromethylphenylsulfonyl)-3,4-dihydrobenzofuro[3,2-c]pyridine-2(1H)-carboxylate

Product 1

HCID 681096516-Chloro-8-(3-trifluoromethylphenylsulfonyl)-1,2,3,4-tetrahydrobenzofuro[3,2-c]pyridine hydrochlorideYield 49.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To the product of step A (130 mg, 0.25 mmol) in dichloromethane, was added trifluoroacetic acid (0.48 mL) at 0° C. After stirring for 3 h, the reaction mixture was concentrated in vacuo, treated with saturated sodium bicarbonate solution and extracted with dichloromethane. The organic extract was dried over sodium sulfate, and concentrated in vacuo. The residue was purified by column chromatography in (SiO2, 90:10 dichloromethane/methanol) and the free base treated directly with 1.25M HCl in methanol to give 6-chloro-8-(3-trifluoromethylphenylsulfonyl)-1,2,3,4-tetrahydrobenzofuro[3,2-c]pyridine hydrochloride (28 mg, 27%) as a white solid: 1H NMR (DMSO-d6, 300 MHz) δ 9.51 (s, 2H), 8.51 (d, J=1.5 Hz, 1H), 8.37-8.34 (m, 2H), 8.18 (d, J=1.5 Hz, 1H), 8.10 (d, J=7.8 Hz, 1H), 7.89 (t, J=7.8 Hz, 1H), 4.38 (s, 2H), 3.52 (t, J=5.2 Hz, 2H), 3.17 (t, J=5.4 Hz, 2H); APCI MS m/z 416 [M+H]+.

Workup

  1. concentrationthe reaction mixture was concentrated in vacuo
  2. additiontreated with saturated sodium bicarbonate solution
  3. extractionextracted with dichloromethane
  4. extractionThe organic extract
  5. dry with materialwas dried over sodium sulfate
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by column chromatography in (SiO2, 90:10 dichloromethane/methanol)
  8. additionthe free base treated directly with 1.25M HCl in methanol

Sources & evidence

ORD record
ord-f5a602f22e134d30b5afec7e21380cc5
Source dataset
uspto-grants-2015_06
Patent number
US09067949B2

Reaction notes

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