Trifluoroacetic acid → (3aR,5R,6aR)-Methyl 2-benzyl-5-((tert-butoxycarbonyl)amino)octahydro-cyclopenta[c]pyrrole-3a-carboxylate

HRID 571350Notes

Reaction equation

HRID 571350 reaction equation
[CH3:1][O:2][C:3]([C:5]1[CH2:9][C@H:8]([NH:10][C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:7][CH:6]=1)=[O:4].CO[CH2:20][N:21]([CH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[CH2:22][Si](C)(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[CH2:27]([N:21]1[CH2:22][C@@:5]2([C:3]([O:2][CH3:1])=[O:4])[CH2:9][C@H:8]([NH:10][C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:7][C@H:6]2[CH2:20]1)[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 353442Benzyl(methoxymethyl)((trimethylsilyl)methyl)amineHCID 10586185methyl (4R)-4-{[(tert-butoxy)carbonyl]amino}cyclopent-1-ene-1-carboxylate

Product 1

HCID 86708893(3aR,5R,6aR)-Methyl 2-benzyl-5-((tert-butoxycarbonyl)amino)octahydro-cyclopenta[c]pyrrole-3a-carboxylate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of the product from Step B (5.51 g, 20 mmol) and N-(methoxymethyl)-N-(trimethylsilylmethyl)benzylamine (6.4 mL, 24 mmol, Aldrich) in DCM (40 mL) was added 1M TFA in DCM (2.4 mL, 2.4 mmol) slowly. The resulting mixture was stirred at rt overnight and quenched by the addition of saturated aqueous NaHCO3 solution. The organic phase was washed with brine, dried over Na2SO4. Evaporation and purification by column chromatography (eluent: 10% EtOAc in hexanes to 20%) gave the desired isomer as a colorless gel. 1H-NMR (400 MHz, CDCl3) of the desired isomer: δ 1.38 (s, 9H), 1.66-1.86 (m, 2H), 1.86-1.96 (m, 1H), 1.96-2.08 (m, 1H), 2.29-2.63 (m, 3H), 2.71-2.93 (m, 2H), 3.43-3.56 (m, 2H), 3.58-3.74 (s, 3H), 4.08-4.29 (m, 1H), 4.78 (d, J=6.6 Hz, 1H), 7.11-7.31 (m, 5H). LC/MS: C24H28N2O4: m/z 375.2 (M+H).

Workup

  1. customquenched by the addition of saturated aqueous NaHCO3 solution
  2. washThe organic phase was washed with brine
  3. dry with materialdried over Na2SO4
  4. customEvaporation and purification by column chromatography (eluent: 10% EtOAc in hexanes to 20%)
  5. customgave the desired isomer as a colorless gel

Sources & evidence

ORD record
ord-d3fa2e254a6c46fe8a5b9f317cd57b4a
Source dataset
uspto-grants-2015_05
Patent number
US09024017B2

Reaction notes

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