1-Hydroxybenzotriazole → N-[(3aS*,4S*,6aR*)-2-benzyloctahydrocyclopenta[c]pyrrol-4-yl]-2,2-dicyclohexylacetamide

HRID 2363440Notes

Reaction equation

HRID 2363440 reaction equation
[CH2:1]([N:8]1[CH2:12][C@H:11]2[CH:13]([NH2:16])[CH2:14][CH2:15][C@H:10]2[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH:17]1([CH:23]([CH:27]2[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]2)[C:24](O)=[O:25])[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]1.ON1C2C=CC=CC=2N=N1.CC[N+](CCCN(C)C)=C=N>ClCCl>[CH2:1]([N:8]1[CH2:12][C@H:11]2[C@@H:13]([NH:16][C:24](=[O:25])[CH:23]([CH:17]3[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]3)[CH:27]3[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]3)[CH2:14][CH2:15][C@H:10]2[CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 3661562Dicyclohexylacetic acidHCID 218833923-(Dimethylamino)propyl-ethyl-(iminomethylidene)azaniumHCID 68411161(3aS*,6aR*)-2-benzyloctahydrocyclopenta[c]pyrrol-4-amine

Product 1

HCID 54674167N-[(3aS*,4S*,6aR*)-2-benzyloctahydrocyclopenta[c]pyrrol-4-yl]-2,2-dicyclohexylacetamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

(3aS*,6aR*)-2-Benzyloctahydrocyclopenta[c]pyrrol-4-amine (500 mg, 2.311 mmol), 2,2-dicyclohexylacetic acid (570 mg, 2.54 mmol), and 1-hydroxybenzotriazole (389 mg, 2.54 mmol) were combined in dichloromethane (20 mL). The reaction was stirred at room temperature for 10 minutes, then N-(3-dimethylaminopropyl)-N-ethylcarbodiimide (0.449 mL, 2.54 mmol) was added dropwise. The reaction was stirred at room temperature for 20 hours, and then the reaction was quenched with 10 mL of water. The reaction mixture was extracted with 2×20 mL of dichloromethane, the solvent was removed in vacuo, and the crude material was chromatographed over a silica gel cartridge (Analogix®, Burlington, Wis., RS-40) eluting with 30-50% ethyl acetate/hexanes to give the title compound as the first eluting diastereomer: 1H NMR (500 MHz, pyridine-d5) δ ppm 7.60 (d, J=5.1, 1H), 7.45-7.38 (m, 4H), 7.35 (m, 1H), 4.49-4.41 (m, 1H), 3.57 (d, J=12.6, 1H), 3.37 (d, J=12.5, 1H), 2.76 (d, J=9.6, 1H), 2.69 (dd, J=7.9, 15.7, 1H), 2.50 (d, J=9.1, 1H), 2.48-2.41 (m, 1H), 2.28 (t, J=8.2, 1H), 2.15-2.08 (m, 1H), 1.99-1.06 (m, 26H), 1.04-0.92 (m, 1H); MS (ESI+) m/z 423 (M+H)+.

Workup

  1. stirringThe reaction was stirred at room temperature for 20 hours
  2. customthe reaction was quenched with 10 mL of water
  3. extractionThe reaction mixture was extracted with 2×20 mL of dichloromethane
  4. customthe solvent was removed in vacuo
  5. customthe crude material was chromatographed over a silica gel cartridge (Analogix®, Burlington, Wis., RS-40)
  6. washeluting with 30-50% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-2da58a8aa75346faa19b44303aabdaae
Source dataset
uspto-grants-2014_04
Patent number
US08691865B2

Reaction notes

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