Benzyl chloroformate → (3aR,5R,6aR)-2-Benzyl 3a-methyl 5-((tert-butoxycarbonyl)amino)-hexahydrocyclopenta[c]pyrrole-2,3a(1H)-dicarboxylate

HRID 571352Notes

Reaction equation

HRID 571352 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@H:9]1[CH2:16][C@H:12]2[CH2:13][NH:14][CH2:15][C@@:11]2([C:17]([O:19][CH3:20])=[O:18])[CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl[C:22]([O:24][CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)=[O:23]>C(Cl)Cl>[C:1]([O:5][C:6]([NH:8][C@@H:9]1[CH2:16][C@H:12]2[CH2:13][N:14]([C:22]([O:24][CH2:25][C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)=[O:23])[CH2:15][C@@:11]2([C:17]([O:19][CH3:20])=[O:18])[CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

4

Reactant 2

HCID 10387Benzyl chloroformateHCID 86708894rac-methyl (3aR,5R,6aR)-5-(((tert-butoxy)carbonyl)amino)-octahydrocyclopenta(c)pyrrole-3a-carboxylate

Product 1

HCID 86708895(3aR,5R,6aR)-2-Benzyl 3a-methyl 5-((tert-butoxycarbonyl)amino)-hexahydrocyclopenta[c]pyrrole-2,3a(1H)-dicarboxylate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of the product from Step D (21.5 g, 75.6 mmol) in DCM (400 mL) was added TEA (31.6 mL, 226.8 mmol) and benzyl chloroformate (14.5 mL, 95%, 98.3 mmol) at 0° C. under Ar. The mixture was stirred at rt for 3 h and quenched by the addition of aqueous NaHCO3 solution. The aqueous phase was extracted with DCM (3×) and the combined organic phases were dried over Na2SO4. Evaporation and purification by column chromatography (eluent: 20% EtOAc in hexanes to 30%) gave the product as a colorless gel. 1H-NMR (400 MHz, CDCl3): δ 1.43 (s, 9H), 1.89 (br. s., 2H), 2.13 (br. s., 2H), 2.99 (d, J=1.0 Hz, 1H), 3.22-3.57 (m, 2H), 3.59-3.83 (m, 4H), 3.99 (d, J=11.6 Hz, 1H), 4.23 (d, J=5.8 Hz, 1H), 4.85 (br. s., 1H), 5.12 (d, J=3.0 Hz, 2H), 7.28-7.42 (m, 5H). LC/MS: C22H30N2O6: m/z 441.2 (M+Na).

Workup

  1. customquenched by the addition of aqueous NaHCO3 solution
  2. extractionThe aqueous phase was extracted with DCM (3×)
  3. dry with materialthe combined organic phases were dried over Na2SO4
  4. customEvaporation and purification by column chromatography (eluent: 20% EtOAc in hexanes to 30%)

Sources & evidence

ORD record
ord-8da8c61a313b48129e16d1d130609902
Source dataset
uspto-grants-2015_05
Patent number
US09024017B2

Reaction notes

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