Hydrochloric Acid → HCID 68108770, compound

HRID 2179426Notes

Reaction equation

HRID 2179426 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([S:23]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)(=[O:25])=[O:24])[C:5]2O[C:13]3[NH:12][CH:11](C(OC(C)(C)C)=O)[CH2:10][CH:9](C)[C:8]=3[C:6]=2[CH:7]=1.[ClH:32].[OH-:33].[Na+].O1CCC[CH2:36]1>CO>[ClH:1].[Cl:32][C:2]1[C:7]2[O:33][C:9]3[CH:10]([CH3:36])[CH2:11][NH:12][CH2:13][C:8]=3[C:6]=2[CH:5]=[C:4]([S:23]([C:26]2[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=2)(=[O:24])=[O:25])[CH:3]=1

Participants

6

Reactant 4

HCID 313Hydrochloric Acid2×HCID 8028TetrahydrofuranHCID 14798Sodium HydroxideHCID 68109336HCID 68109336, compound

Product 1

HCID 68108770HCID 68108770, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Procedure

To a solution of the product of step C (190 mg, 0.41 mmol) in tetrahydrofuran (10 mL) was added conc. hydrochloric acid (1.2 mL, 12.34 mmol) at ambient temperature. After 15 h, the reaction was basified with 10% NaOH solution and extracted with dichloromethane. The organic layer was concentrated in vacuo and the residue purified by flash column chromatography (SiO2, 95:5 dichloromethane/methanol) to provide the free base which was converted directly to the hydrochloride salt by dissolving in methanol and treating with 1.25 M HCl in methanol. Concentration in vacuo afforded 6-chloro-4-methyl-8-(phenylsulfonyl)-1,2,3,4-tetrahydrobenzofuro[3,2-c]pyridine hydrochloride (70 mg, 48%, AUC HPLC 96.8%) as a white solid: mp 291-292° C. dec; 1H NMR (DMSO-d6, 400 MHz) δ 9.72 (br s, 2H), 8.43 (s, 1H), 8.09-7.99 (m, 3H), 7.74-7.59 (m, 3H), 4.49-4.28 (m, 2H), 3.71-3.44 (m, 2H), 3.19-3.11 (m, 1H), 1.35 (d, J=4.8 Hz, 3H); APCI MS m/z 362 [M+H]+.

Workup

  1. extractionextracted with dichloromethane
  2. concentrationThe organic layer was concentrated in vacuo
  3. customthe residue purified by flash column chromatography (SiO2, 95:5 dichloromethane/methanol)
  4. customto provide the free base which
  5. concentrationConcentration in vacuo

Sources & evidence

ORD record
ord-98ccac92d39c4e52bcf1801945f74cf7
Source dataset
uspto-grants-2015_06
Patent number
US09067949B2

Reaction notes

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