Hydrochloric Acid → 4-((N-benzyl-4-methylphenylsulfonamido)methyl)cyclohexanecarboxylic acid

To the mixture of the HCl salt of methyl 4-(aminomethyl)cyclohexanecarboxylate (208 mg, 1 mmol) in 5 mL of dichloromethane, at 0° C. in an ice bath, were added triethylamine (360 uL, 2.58 mmol) and 4-methylbenzene-1-sulfonyl chloride (190 mg, 1 mmol). The ice bath was allowed to warm slowly to ambient temperature and stirred overnight. The solvent was removed in vacuo. The residue was re-dissolved in ethyl acetate (20 mL), washed with 1N HCl (5 mL), water (5 mL) and brine (5 mL), then dried over magnesium sulfate and concentrated. This crude product (162 mg, 0.5 mmol) was redissolved in acetone (5 mL) and treated with potassium carbonate (110 mg, 0.79 mmol) and (4-fluorophenyl)methanamine (1.76 mL, 14.08 mmol). The mixture was stirred in a pressure vessel at 80° C. overnight, then cooled and the inorganic salts were filtered off. Acetone was removed in vacuo and the residue was re-dissolved in ethyl acetate and washed with water followed by brine. The organic layer was dried over magnesium sulfate and concentrated. The crude product (162 mg, 0.4 mmol) was dissolved in MeOH/THF (1:1.5, 10 mL) and treated with aqueous NaOH (10N, 400 uL). The mixture was stirred at 100° C. for 20 min in a microwave, and then MeOH and THF were removed in vacuo. The residue was acidified with 6 N aq HCl to a pH of ˜3 and extracted with EtOAc; the combined organic layers were washed with water and brine, dried over Na2SO4 and concentrated. The crude product was purified by recrystallization from EtOH to afford pure 4-((N-benzyl-4-methylphenylsulfonamido)methyl)cyclohexanecarboxylic acid as a white solid (120 mg, 74%). MS (M+H, 402); 1H NMR (400 MHz, DMSO-d6): δ, ppm: 0.68 (m, 2H)), 0.91 (m, 2H), 1.06 (br, s, 1H), 1.50 (d, 2H), 1.72 (d, 2H), 2.0 (1H), 2.41 (s, 3H), 2.86 (m, 2H), 4.21 (s, 2H), 7.30 (m, 5H), 7.43 (m, 2H), 7.73 (m, 2H), 11.97 (br, s, 1H).

1. customThe solvent was removed in vacuo
2. dissolutionThe residue was re-dissolved in ethyl acetate (20 mL)
3. washwashed with 1N HCl (5 mL), water (5 mL) and brine (5 mL)
4. dry with materialdried over magnesium sulfate
5. concentrationconcentrated
6. stirringThe mixture was stirred in a pressure vessel at 80° C. overnight
7. temperaturecooled
8. filtrationthe inorganic salts were filtered off
9. customAcetone was removed in vacuo
10. dissolutionthe residue was re-dissolved in ethyl acetate
11. washwashed with water
12. dry with materialThe organic layer was dried over magnesium sulfate
13. concentrationconcentrated
14. stirringThe mixture was stirred at 100° C. for 20 min in a microwave
15. customMeOH and THF were removed in vacuo
16. extractionextracted with EtOAc
17. washthe combined organic layers were washed with water and brine
18. dry with materialdried over Na2SO4
19. concentrationconcentrated
20. customThe crude product was purified by recrystallization from EtOH

ORDレコード

ord-9830712a58dc40498b8d633e9905a01f

出典データセット

uspto-grants-2016_02

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US09247759B2