TRANS-3-CBZ-AMINOCYCLOBUTANECARBOXYLIC ACID synthesis

Yield:1398571-06-6 45%

Reaction Conditions:

Stage #1: trans-3-{[(benzyloxy)carbonyl]amino}cyclobutanecarboxylic acidwith triethylamine;isobutyl chloroformate in tetrahydrofuran; for 0.166667 h;Cooling with ice;
Stage #2: with sodium tetrahydroborate in methanol;Cooling with ice;

Steps:

55.1

Isobutyl chloroformate (0.14 ml, 1.04 mmol) and triethylamine (0.15 ml, 1.04 mmol) were added in that order to a tetrahydrofuran (4 ml) solution of the same starting material (260 mg, 1.04 mmol) as in Step 1 of Reference Example 51 under ice cooling, and the resulting mixture was stirred at the same temperature for 10 minutes. Insoluble matter was removed by filtration through celite, methanol (1 ml) was added to the filtrate and sodium borohydride (79 mg, 2.09 mmol) was added under ice cooling. After stirring for 30 minutes, 1N hydrochloric acid was added. The solvent was evaporated under reduced pressure, the residue was subjected to extraction with ethyl acetate and the organic layer was washed with brine and then dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure and the residue was purified by silica gel column chromatography [n-hexane:ethyl acetate=3:1→1:1 (v/v)] to give 111 mg (45%) of the title compound as a colorless solid.¹H-NMR (400 MHz, CDCl₃) δ: 1.36 (1H, br s), 1.95-2.08 (2H, m), 2.15-2.27 (2H, m), 2.32-2.47 (1H, m), 3.68 (2H, d, J=7.3 Hz), 4.17-4.33 (1H, m), 4.93 (1H, br s), 5.08 (2H, s), 7.29-7.39 (5H, m).MS (ESI) m/z: 236 (M+H)⁺.

References:

US2012/264738,2012,A1 Location in patent:Page/Page column 151