HCID 15454897, compound → HCID 70300060, compound

HRID 2287522Notes

Reaction equation

HRID 2287522 reaction equation
C(OC([N:11]1[C@H:15]([CH3:16])[C@@H:14]([C:17]([O:19][CH3:20])=[O:18])[C@H:13]([NH:21][CH2:22][C:23]2[CH:28]=[C:27]([O:29][C:30]([F:33])([F:32])[F:31])[CH:26]=[CH:25][C:24]=2[O:34][CH3:35])[C@@H:12]1[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1)=O)C1C=CC=CC=1.COC1C=CC(OC(F)(F)F)=CC=1CN[C@H]1[C@H](C(OC)=O)[C@@H](C)N[C@H]1C1C=CC=CC=1>CO.[OH-].[OH-].[Pd+2]>[CH3:35][O:34][C:24]1[CH:25]=[CH:26][C:27]([O:29][C:30]([F:31])([F:33])[F:32])=[CH:28][C:23]=1[CH2:22][NH:21][C@H:13]1[C@@H:14]([C:17]([O:19][CH3:20])=[O:18])[C@@H:15]([CH3:16])[NH:11][C@H:12]1[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1

Participants

5

Reactant 2

HCID 15454897HCID 15454897, compound2×HCID 70301949HCID 70301949, compound

Product 1

HCID 70300060HCID 70300060, compoundYield 27.3%

Reagents, catalysts & solvents 2

HCID 9942167Palladium hydroxideCatalystHCID 887MethanolSolvent

Procedure

20% Pd(OH)2 --C (Pearlman's cat., 600 mg) was added to a solution of (2S*,3S*,4S*,5R*)-1-benzyloxycarbonyl-3-[N-(2-methoxy-5-trifluoromethoxybenzyl)amino]-4-methoxycarbonyl-5-methyl-2-phenylpyrrolidine 1.08 g, 1.89 mmol) and HCO2NH4 (714 mg, 11.3 mmol) in methanol (25 ml). The reaction mixture was stirred and heated at a gentle reflux for 30 min. The catalyst was filtered off by the aid of a Celite pad, and washed with MeOH. The combined filtrate and washings were concentrated in vacuo. The residue was basified to pH 10-11 with 10% NaOH aq. solution, and extracted with CH2Cl2 (60 ml×4). The combined CH2Cl2 extracts were washed with brine, dried (MgSO4) and concentrated in vacuo to give a crude mixture of (2S*,3S*,4R*,5R*)-3-[N-(2-methoxy-5-trifluoromethoxybenzyl)amino]-4-methoxycarbonyl-5-methyl-2-phenylpyrrolidine and (2S*,3S*,4R*,5R*)-3-[N-(2-methoxy-5-trifluoromethoxybenzyl)amino]-4-methoxycarbonyl-5-methyl-2-phenylpyrrolidine (794 mg) as a yellow oil. This was purified by column chromatography on silica gel (45 g) with hexane-ethyl acetate (1:1) to give (2S*,3S*,4S*,5R*)-3-[N-(2-methoxy-5-trifluoromethoxybenzyl)amino]-4-methoxycarbonyl-5-methyl-2-phenylpyrrolidine (222 mg, 27.3%) as a pale yellow solid, which was recrystallized from hexane-ethyl acetate to give (2S*,3S*,4S*,5R*)-3-[N-(2-methoxy-5-trifluoromethoxybenzyl)-amino]-4-methoxycarbonyl-5-methyl-2-phenylpyrrolidine (127 mg, 1st crop) as a white solid: mp 81-82° C.

Workup

  1. temperatureheated at
  2. temperaturea gentle reflux for 30 min
  3. filtrationThe catalyst was filtered off by the aid of a Celite pad
  4. washwashed with MeOH
  5. concentrationThe combined filtrate and washings were concentrated in vacuo
  6. extractionextracted with CH2Cl2 (60 ml×4)
  7. washThe combined CH2Cl2 extracts were washed with brine
  8. dry with materialdried (MgSO4)
  9. concentrationconcentrated in vacuo
  10. customto give a crude
  11. customThis was purified by column chromatography on silica gel (45 g) with hexane-ethyl acetate (1:1)

Sources & evidence

ORD record
ord-621605ba73074ea8a75db289b7467c62
Source dataset
uspto-grants-2000_07
Patent number
US06083943

Reaction notes

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