Benzyl chloroformate → trans-3-(3-Cyclopentoxy-4-methoxyphenyl)-4-methoxycarbonyl-1-(phenylmethoxycarbonyl)pyrrolidine

HRID 1377770Notes

Reaction equation

HRID 1377770 reaction equation
[CH:1]1([O:6][C:7]2[CH:8]=[C:9]([C@H:15]3[C@H:19]([C:20]([O:22][CH3:23])=[O:21])[CH2:18][N:17](CC4C=CC=CC=4)[CH2:16]3)[CH:10]=[CH:11][C:12]=2[O:13][CH3:14])[CH2:5][CH2:4][CH2:3][CH2:2]1.Cl[C:32]([O:34][CH2:35][C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1)=[O:33]>C(O)=O.CO.C(Cl)Cl.CN(C1C=CN=CC=1)C.[Pd]>[CH:1]1([O:6][C:7]2[CH:8]=[C:9]([C@H:15]3[C@H:19]([C:20]([O:22][CH3:23])=[O:21])[CH2:18][N:17]([C:32]([O:34][CH2:35][C:36]4[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=4)=[O:33])[CH2:16]3)[CH:10]=[CH:11][C:12]=2[O:13][CH3:14])[CH2:2][CH2:3][CH2:4][CH2:5]1

Participants

8

Reactant 2

HCID 10387Benzyl chloroformateHCID 70091886trans-3-(3-Cyclopentoxy-4-methoxyphenyl)-4-methoxycarbonyl-1-(phenylmethyl)pyrrolidine

Product 1

HCID 44302345trans-3-(3-Cyclopentoxy-4-methoxyphenyl)-4-methoxycarbonyl-1-(phenylmethoxycarbonyl)pyrrolidineYield 40%

Reagents, catalysts & solvents 5

HCID 142844-(Dimethylamino)pyridineCatalystHCID 23938PalladiumCatalystHCID 284Formic AcidSolventHCID 887MethanolSolvent2×HCID 6344DichloromethaneSolvent

Procedure

trans-3-(3-Cyclopentoxy-4-methoxyphenyl)-4-methoxycarbonyl-1-(phenylmethyl)pyrrolidine (3.1 g, 7.5 mmol) was dissolved in 50 mL of 4% HCO2H:methanol. While stirring at room temperature, 10% Pd/C (400 mg) was added in small portions. After 16 hrs the reaction was diluted with methanol. Filtration through Celite followed by concentration under reduced pressure yielded a yellow oil residue. This residue was dissolved in CH2Cl2 and DMAP (1.19 g, 9.75 mmol) and benzyl chloroformate (1.5 g, 8.2 mmol) were added. The resulting solution was stirred at room temperature. When reaction was judged complete by TLC analysis the mixture was partitioned between CH2Cl2 and 1M H3PO4. The layers were separated and the aqueous layer was extracted with CH2Cl2 (2×). The organic layers were combined, dried (MgSO4), filtered, and concentrated under reduced pressure to afford a pale oil. Chromatography on silica gel (3:2, hexanes:ethyl acetate) provided trans-3-(3-cyclopentoxy-4-methoxyphenyl)-4-methoxycarbonyl-1-(phenylmethoxycarbonyl)pyrrolidine as a white solid (1.34 g, 40%). m.p. 85° C. Anal. Calcd for C26H31NO6 : C, 68.86; H, 6.89; N, 3.09. Found: C, 68.81; H, 6.94; N, 2.99.

Workup

  1. filtrationFiltration through Celite
  2. concentrationfollowed by concentration under reduced pressure
  3. customyielded a yellow oil residue
  4. stirringThe resulting solution was stirred at room temperature
  5. customWhen reaction
  6. customwas partitioned between CH2Cl2 and 1M H3PO4
  7. customThe layers were separated
  8. extractionthe aqueous layer was extracted with CH2Cl2 (2×)
  9. dry with materialdried (MgSO4)
  10. filtrationfiltered
  11. concentrationconcentrated under reduced pressure
  12. customto afford a pale oil

Sources & evidence

ORD record
ord-8a25bf0b489047ca8793c1c9d43cbbc2
Source dataset
uspto-grants-1997_09
Patent number
US05665754

Reaction notes

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