Water → (2S,4S)-4-(4-methoxybenzyl)thio-1-(4-nitrobenzyloxycarbonyl)-L-proline

HRID 362082Notes

Reaction equation

HRID 362082 reaction equation
[CH3:1][O:2][C:3]1[CH:18]=[CH:17][C:6]([CH2:7][S:8][C@@H:9]2[CH2:13][NH:12][C@H:11]([C:14]([OH:16])=[O:15])[CH2:10]2)=[CH:5][CH:4]=1.O.[OH-].[Na+].[N+:22]([C:25]1[CH:35]=[CH:34][C:28]([CH2:29][O:30][C:31](Cl)=[O:32])=[CH:27][CH:26]=1)([O-:24])=[O:23]>O1CCCC1>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([CH2:7][S:8][C@@H:9]2[CH2:13][N:12]([C:31]([O:30][CH2:29][C:28]3[CH:27]=[CH:26][C:25]([N+:22]([O-:24])=[O:23])=[CH:35][CH:34]=3)=[O:32])[C@H:11]([C:14]([OH:16])=[O:15])[CH2:10]2)=[CH:17][CH:18]=1

Participants

6

Reactant 4

HCID 962WaterHCID 14798Sodium Hydroxide2×HCID 782054-Nitrobenzyl chloroformateHCID 15297070(4S)-4-{[(4-Methoxyphenyl)methyl]sulfanyl}-L-proline

Product 1

HCID 15297071(2S,4S)-4-(4-methoxybenzyl)thio-1-(4-nitrobenzyloxycarbonyl)-L-prolineYield 77.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A suspension of 1.87 g of (2S,4S)-4-(4-methoxybenzylthio)-2-pyrrolidinecarboxylic acid [prepared as described in step (i) above] in 80 ml of a 1:1 by volume mixture of tetrahydrofuran and water was transformed to a homogeneous solution by adding 7 ml of a 1N aqueous solution of sodium hydroxide. The solution was ice-cooled and stirred, and, little by little, a solution of 1510 mg of 4-nitrobenzyloxycarbonyl chloride in 10 ml of tetrahydrofuran and 7 ml of a 1N aqueous solution of sodium hydroxide were simultaneously added dropwise. The resulting mixture was stirred at the same temperature for 10 minutes. At the end of this time, the reaction mixture was freed from tetrahydrofuran by distillation under reduced pressure, and its pH was adjusted to a value of between 2 and 3 by the addition of 1N aqueous hydrochloric acid. The crystals which precipitated were collected by filtration, washed well with water and subjected to air-drying. The crystals were further washed with a small amount of diethyl ether and dried, to give 2.42 g of the title compound, melting at 96°-98° C.

Workup

  1. temperaturecooled
  2. stirringThe resulting mixture was stirred at the same temperature for 10 minutes
  3. distillationAt the end of this time, the reaction mixture was freed from tetrahydrofuran by distillation under reduced pressure, and its pH
  4. additionwas adjusted to a value of between 2 and 3 by the addition of 1N aqueous hydrochloric acid
  5. customThe crystals which precipitated
  6. filtrationwere collected by filtration
  7. washwashed well with water
  8. customto air-drying
  9. washThe crystals were further washed with a small amount of diethyl ether
  10. customdried

Sources & evidence

ORD record
ord-641d786b8ed34b71a0797203081dd0e3
Source dataset
uspto-grants-1999_02
Patent number
US05866564

Reaction notes

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