Allyl chloroformate → 4-Hydroxy-1-[(prop-2-en-1-yloxy)carbonyl]pyrrolidine-2-carboxylic acid
Reaction equation
[OH:1][CH:2]1[CH2:6][NH:5][C@H:4]([C:7]([OH:9])=[O:8])[CH2:3]1.Cl[C:11]([O:13][CH2:14][CH:15]=[CH2:16])=[O:12]>[OH-].[Na+].O1CCOCC1>[CH2:14]([O:13][C:11]([N:5]1[CH2:6][CH:2]([OH:1])[CH2:3][CH:4]1[C:7]([OH:9])=[O:8])=[O:12])[CH:15]=[CH2:16]Participants
Procedure
To a solution of 4-hydroxyproline (0.25M) in 4N sodium hydroxide (78ml), at 0°-5° C., was added allyl chloroformate (0.31M) in dioxan (156 ml) and 4N sodium hydroxide (78 ml). The dioxan solution and sodium hydroxide were added simultaneously, in batches, allowing the temperature to return to below 5° C. after each addition. The mixture was stirred for a further hour, washed with ethyl acetate, acidified (conc. HCl) and extracted into ethyl acetate. The organic phase was washed with brine, dried and evaporated to give 1-allyloxycarbonyl-4-hydroxypyrrolidine-2-carboxylic acid as a viscous syrup. This (0.1M) was treated with 4-methoxybenzyl chloride (0.19M) and triethylamine (0.2M) in DMF (200 ml), under argon, at 70° C. for 10 hours. Ethyl acetate was added and the mixture was washed with water and brine and evaporated to give a gum. This was subjected to medium pressure chromatography (gradient elution with ether to ether/1% methanol) to give 4-methoxybenzyl 1-allyloxycarbonyl-4-hydroxy-pyrrolidine-2-carboxylate.
Workup
- customto return to below 5° C.
- additionafter each addition
- washwashed with ethyl acetate
- extractionextracted into ethyl acetate
- washThe organic phase was washed with brine
- customdried
- customevaporated
Sources & evidence
- ORD record
- ord-9ab13913208d4291a260a237234ec5d8
- Source dataset
- uspto-grants-1996_09
- Patent number
- US05554606
Reaction notes
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