Citric Acid → HCID 10970865, compound

HRID 263757Notes

Reaction equation

HRID 263757 reaction equation
[C:1]([NH:8][C@H:9]([C@H:17]1[O:21][C:20](=[O:22])[CH:19]([C:23]([O:25][CH2:26][CH3:27])=[O:24])[CH2:18]1)[CH2:10][CH:11]1[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].FC1C=CC(CBr)=CC=1.[Na].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C(O)C>[C:1]([NH:8][C@H:9]([C@H:17]1[O:21][C:20](=[O:22])[CH:19]([C:23]([O:25][CH2:26][CH3:27])=[O:24])[CH2:18]1)[CH2:10][C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1)([O:3][C:4]([CH3:6])([CH3:5])[CH3:7])=[O:2]

Participants

6

Reactant 4

HCID 311Citric AcidHCID 680214-Fluorobenzyl bromide2×HCID 5360545Sodium2×HCID 131720079HCID 131720079, compound

Product 1

HCID 10970865HCID 10970865, compound

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

10.2 g of 5(S)-[1(S)-(Boc-amino)-2-cyclohexylethyl]-3(R,S)-ethoxycarbonyl-dihydrofuran-2-(3H)-one are reacted at RT with 5.39 g of p-fluorobenzyl bromide (Fluka, Buchs, Switzerland) and 0.68 g of sodium in 180 ml of ethanol. Because, according to TLC, not all of the lactone has reacted after 1.5 h, a further 0.2 g of sodium and 0.7 g of p-fluorobenzyl bromide are added. After 16 h, the batch is poured onto a mixture of 10% citric acid and ice and extracted 3 times with ether. The organic phases are washed twice with water and twice with brine, dried with Na2SO4 and concentrated by evaporation. After the addition of hexane/ethyl acetate, some of the oily crude product crystallises out under the effect of ultrasound to give the title compound (ratio of diastereoisomers 4:1). Column chromatography (SiO2, hexane/ethyl acetate 4:1) of the mother liquor yields more title compound (ratio of diastereoisomers approximately 1:4). TLC Rf (C)=0.29; FAB-MS (M+H)+ =492.

Workup

  1. extractionextracted 3 times with ether
  2. washThe organic phases are washed twice with water and twice with brine
  3. dry with materialdried with Na2SO4
  4. concentrationconcentrated by evaporation
  5. additionAfter the addition of hexane/ethyl acetate
  6. customsome of the oily crude product crystallises out under the effect of ultrasound

Sources & evidence

ORD record
ord-7b847615c2744b168ac88bbf964febb9
Source dataset
uspto-grants-1997_07
Patent number
US05643878

Reaction notes

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