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

HRID 1684703Notes

Reaction equation

HRID 1684703 reaction equation
[CH:1]12[CH2:7][CH:4]([CH:5]=[CH:6]1)[C:3](=[O:8])[NH:2]2.[CH3:9][S:10]([OH:13])(=[O:12])=[O:11].[OH2:14]>>[CH3:9][S:10]([OH:13])(=[O:12])=[O:11].[NH2:2][C@@H:1]1[CH2:7][C@H:4]([C:3]([OH:8])=[O:14])[CH:5]=[CH:6]1

Participants

4

Reactant 3

HCID 962WaterHCID 6395Methanesulfonic AcidHCID 5486782-Azabicyclo(2.2.1)hept-5-en-3-one

Product 1

HCID 15451704(-)-(1S,4R)-4-Amino-2-cyclopentene-1-carboxylic acid methanesulfonateYield 0.6%

Conditions

Temperature
35 °C

Procedure

A solution of (-)-2-azabicyclo[2.2.1]hept-5-en-3-one (97.45 g, 0.8929 mol, Enzymatix Ltd.) in tetrahydr n (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); Cl-MS (CH4): 128(M+1); El-MS: 127(M).

Workup

  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

Sources & evidence

ORD record
ord-97c854bcd13b40fe8219a3bfd9c2a5f2
Source dataset
uspto-grants-1997_06
Patent number
US05641889

Reaction notes

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