Methanol → (2S,4R)-1-allyloxycarbonyl-2-methoxycarbonyl-4-hydroxypyrrolidine

HRID 1826103Notes

Reaction equation

HRID 1826103 reaction equation
OS(O)(=O)=O.[CH2:6]([O:9][C:10]([N:12]1[CH2:16][C@H:15]([OH:17])[CH2:14][C@H:13]1[C:18]([OH:20])=[O:19])=[O:11])[CH:7]=[CH2:8].[CH3:21]O>>[CH2:6]([O:9][C:10]([N:12]1[CH2:16][C@H:15]([OH:17])[CH2:14][C@H:13]1[C:18]([O:20][CH3:21])=[O:19])=[O:11])[CH:7]=[CH2:8]

Participants

4

Reactant 3

HCID 887MethanolHCID 1118Sulfuric AcidHCID 18639171(2S,4R)-1-allyloxycarbonyl-2-carboxy-4-hydroxypyrrolidine

Product 1

HCID 10633157(2S,4R)-1-allyloxycarbonyl-2-methoxycarbonyl-4-hydroxypyrrolidineYield 43%

Procedure

A catalytic amount of concentrated H2SO4 (4.5 mL) was added to a solution of Alloc-hydroxyproline (12) (43 g, 200 mmol) in MeOH (300 mL) at 10° C. (ice) and the reaction mixture was then heated at reflux for 2 h. After cooling to room temperature the reaction mixture was treated with TEA (43 mL) and the MeOH evaporated in vacuo. The residue was dissolved in EtOAc (300 mL), washed with brine (200 mL), dried (MgSO4), filtered and concentrated in vacuo to give a viscous oil. Purification by flash chromatography (40% EtOAc/Petroleum Ether) removed the high R1 impurity to provide the pure ester 13 as a transparent yellow oil (19.6 g, 43%): [α]23D=−79.0° (c 0.35, CHCl3); 1H NMR (270 MHz, CDCl3) (Rotamers) δ 5.98-5.78 (m, 1H, NCO2CH2CH═CH2), 5.35-5.16 (m, 2H, NCO2CH2CH═CH3), 4.65-4.45 (m, 4H, NCO2CH2CH═CH2, NCH2CHOHCH2 and NCHCO2CH3), 3.75 and 3.72 (s×2, 3H, OCH3), 3.70-3.54 (m, 2H, NCH2CHOHCH2), 3.13 and 3.01 (br s×2, 1H, OH), 2.39-2.03 (m, 2H, NCH2CHOHCH2); 13C NMR (67.8 MHz, CDCl3) (Rotamers) δ 173.4 and 173.2 (CO2CH3), 155.0 and 154.6 (NC═O), 132.6 and 132.4 (NCO2CH2CH═CH2), 117.6 and 117.3 (NCO7CH2CH═CH2), 70.0 and 69.2 (NCH2CHOH), 66.2 (NCO2CH2CH═CH2), 57.9 and 57.7 (NCHCO2CH3), 55.2 and 54.6 (NCH2CHOH), 52.4 (OCH3), 39.1 and 38.4 (NCH2CHOHCH2); MS (EI), m/z (relative intensity) 229 (M+., 7), 170 (M-CO2Me, 100), 144 (M-CO2C3H5, 12), 126 (26), 108 (20), 68 (7), 56 (8); IR (Neat) 3438 (br, OH), 2954, 1750 and 1694 (br, C═O), 1435, 1413, 1345, 1278, 1206, 1130, 1086, 994, 771 cm−1; exact mass calcd for C10H15NO5 m/e 229.0950, obsd m/e 229.0940.

Workup

  1. temperaturethe reaction mixture was then heated
  2. temperatureat reflux for 2 h
  3. customthe MeOH evaporated in vacuo
  4. dissolutionThe residue was dissolved in EtOAc (300 mL)
  5. washwashed with brine (200 mL)
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customto give a viscous oil
  10. customPurification by flash chromatography (40% EtOAc/Petroleum Ether)
  11. customremoved the high R1 impurity

Sources & evidence

ORD record
ord-9c44ce406a2e49e3bc30722ffdb908e8
Source dataset
uspto-grants-2006_05
Patent number
US07049311B1

Reaction notes

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