Water → (-)-(1S,4R)-4-Amino-2-cyclopentene-1-carboxylic acid methanesulfonate

Temperature

35 °C

A solution of (-)-2-azabicyclo[2.2.1]hept-5-en-3-one (97.45 g, 0.8929 mol, Enzymatix Ltd.) in tetrahydrofuran (500 mL) was filtered and warmed to 35° C. A solution of methanesulfonic acid (63.7 mL, 0.9817 mol) in water (24.1 mL, 1.34 mol) was added over the course of 1.5 hours such that the ensuing exotherm did not exceed 45° C. The resulting slurry was heated at 60° C. for three hours, then allowed to cool to room temperature over the course of 15 hours. The slurry was filtered and the cake washed twice with anhydrous tetrahydrofuran (200 mL). An analytical sample of the wet cake was removed and dried to give the title compound as a white solid (1.264 g); m.p. 167°-169.2° C.; 1H-NMR (DMSO-d6) δ: 12.6 (br s, 1H, CO2H), 8.04 (br s, 3H, NH3+), 6.10 (dt, J=5.6, 2.0, 2.0 Hz, 1H, vinyl), 5.85 (dt, J=5.3, 2.3, 2.3 Hz, 1H, vinyl), 4.19 (br s, w1/2=20 Hz, 1H, allylic H), 3.61 (m, w1/2=22 Hz, 1H, allylic H), 2.53 (quintet, J=5.3 Hz (overlapping with DMSO peak), 1/2CH2), 2.39 (s, 3H, CH3SO3H), 1.93 (dt, J=6.7, 6.7, 13.7 Hz, 1H, 1/2CH2); [α]20589 -83.8°, [α]20578 -87.4°, [α]20546 -101.2°, [α]20436 -186.7°, [α]20365 -316.2° (c=1.42, methanol); CI-MS (CH4): 128(M+1); EI-MS: 127(M).

1. customdid not exceed 45° C
2. temperatureThe resulting slurry was heated at 60° C. for three hours
3. temperatureto cool to room temperature over the course of 15 hours
4. filtrationThe slurry was filtered
5. washthe cake washed twice with anhydrous tetrahydrofuran (200 mL)
6. customAn analytical sample of the wet cake was removed
7. customdried

ORD record

ord-8a19c9ff693b409aba961ebfed2a2155

Source dataset

uspto-grants-1995_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05399580