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

HRID 1034527Notes

Reaction equation

HRID 1034527 reaction equation
Cl.[OH:2][C@H:3]1[CH2:7][NH:6][C@H:5]([C:8]([O:10][CH3:11])=[O:9])[CH2:4]1.C(N(CC)CC)C.Cl[C:20]([O:22][CH2:23][CH:24]=[CH2:25])=[O:21]>ClCCl.O>[CH2:23]([O:22][C:20]([N:6]1[CH2:7][C@H:3]([OH:2])[CH2:4][C@H:5]1[C:8]([O:10][CH3:11])=[O:9])=[O:21])[CH:24]=[CH2:25]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 18052Allyl chloroformateHCID 114353194-Hydroxy-L-proline methyl ester hydrochloride

Product 1

HCID 10633157(2S,4R)-1-allyloxycarbonyl-2-methoxycarbonyl-4-hydroxypyrrolidineYield 95.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a suspension of (2S,4R)-4-hydroxy-2-methoxycarbonylpyrrolidine hydrochloride (17.0 g: 100 mmole) in dichloromethane (200 ml), triethylamine (29.2 ml: 210 mmole) is added in a nitrogen atmosphere under ice cooling. The mixture is stirred for 5 minutes at room temperature, mixed dropwise with a solution of allyl chloroformate (11.2 ml: 100 mmole) in dichloromethane (20 ml), stirred for 1 hour at room temperature, and diluted with water (250 ml). The organic layer is taken, successively washed with water and saturated brine, dried over magnesium sulfate, and concentrated in vacuo to give (2S,4R)-1-allyloxycarbonyl-4-hydroxy-2-methoxycarbonylpyrrolidine (21.82 g) as oil. To a solution of this product in dichloromethane (100 ml), triethylamine (16.7 ml: 120 mmole) and methanesulfonylchloride (9.2 ml: 120 mmole) are added in a nitrogen atmosphere under ice cooling, and the mixture is stirred for 10 minutes. The reaction mixture is successively washed with aqueous sodium hydrogen carbonate and saturated brine, dried over magnesium sulfate, concentrated in vacuo, and purified by silica gel chromatography (tolueneethyl acetate) to give (2S, 4R)-1-allyloxycarbonyl-4-methanesulfonyloxy-2-methoxycarbonylpyrrolidine (27.62 g) as oil. Yield: 90%. NMR δ(CDCl3) ppm: 2.2 to 2.4(m, 1H), 2.2 to 2.5(m, 1H), 2.5 to 2.8(m, 2H), 3.06(s, 3H), 3.74 & 3.77(2×s, 3H), 3.8 to 4.0(m, 2H), 4.4 to 4.7(m, 3H), 5.2 to 5.4(m, 3H), 5.8 to 6.0(m, 1H).

Workup

  1. additionis added in a nitrogen atmosphere under ice cooling
  2. stirringstirred for 1 hour at room temperature
  3. washsuccessively washed with water and saturated brine
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-61074f90e98642dc9813eca5dc93387d
Source dataset
uspto-grants-1994_05
Patent number
US05317016

Reaction notes

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