Hydrochloric Acid → (+/-)-4-[Amino-(3,3-dimethyl-cyclobutyl)-methyl]-benzoic acid ethyl ester

Participants

Reaction Conditions

Reaction Steps

4-(3,3-dimethyl-cyclobutanecarbonyl)-benzoic acid ethyl ester (Intermediate 23) (235 mg, 0.903 mmol) was dissolved in methanol (5 mL). Ammonium acetate (710 mg, 9.03 mmol) was added followed by sodium cyanoborohydride (89.6 mg, 1.36 mmol). This was heated to 60° C. for 17 h before cooling and adding 1 N HCl (3 mL). This was stirred for 15 min and then 1N NaOH (10 mL) was added. The material was extracted into two portions of ethyl acetate and the combined organics dried over MgSO4. Purification by silica gel flash chromatography (methanol/ethyl acetate) gave (+/−)-4-[amino-(3,3-dimethyl-cyclobutyl)-methyl]-benzoic acid ethyl ester (137 mg) as a pale yellow oil. 1H NMR (400 MHz, CDCl3) δ 7.99 (d, J=8.4 Hz, 2H) 7.37 (d, J=8.2 Hz, 2H) 4.38 (q, J=7.0 Hz, 2H) 3.82 (d, J=9.2 Hz, 1H) 2.39 (sxt, J=8.7 Hz, 1H) 1.90-2.02 (m, 1H) 1.60-1.70 (m, 1H) 1.46-1.57 (m, 2H) 1.40 (t, J=7.1 Hz, 3H) 1.11 (s, 3H) 1.06 (s, 3H); GCMS (M): 261.

Provenance & Evidence