Citric Acid → HCID 67490989, compound

HRID 1917325Notes

Reaction equation

HRID 1917325 reaction equation
[BH4-].[Li+].C([O:5][C:6]([C:8]1([C@H:11]2[CH2:15][C:14](=[O:16])[N:13]([C@H:17]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[CH3:18])[CH2:12]2)[CH2:10][CH2:9]1)=O)C.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>O1CCCC1>[OH:5][CH2:6][C:8]1([C@H:11]2[CH2:15][C:14](=[O:16])[N:13]([C@H:17]([C:19]3[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=3)[CH3:18])[CH2:12]2)[CH2:9][CH2:10]1

Participants

5

Reactant 3

HCID 311Citric AcidHCID 4148881Lithium borohydrideHCID 10924617HCID 10924617, compound

Product 1

HCID 67490989HCID 67490989, compoundYield 74%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

Lithium borohydride (1.174 g, 53.90 mmol) was added to a solution of 1-[(3R)-5-oxo-1-[(1S)-1-phenylethyl]pyrrolidin-3-yl]cyclopropanecarboxylic acid ethyl ester [see Journal of Medicinal Chemistry, Vol. 46, No. 6, p. 1005 (2003)] (2.03 g, 6.74 mmol) in tetrahydrofuran (20 mL). The mixture was heated with stirring on an oil bath at 70° C. for 30 hours. After cooling to room temperature, the reaction solution was poured into an ice-cooled 10% citric acid solution (80 mL), followed by extraction with ethyl acetate (200 mL). The organic layer was washed with water (80 mL) and brine (80 mL), dried over anhydrous sodium sulfate, and then filtered, and the solvent was evaporated under reduced pressure. The resulting residue was purified by silica gel column chromatography (ethyl acetate:hexane=1:2→1:1→2:1→1:0→chloroform:methanol=9:1) to give 1.30 g (74%) of the title compound as a colorless transparent gummy solid.

Workup

  1. temperatureThe mixture was heated
  2. temperatureAfter cooling to room temperature
  3. extractionfollowed by extraction with ethyl acetate (200 mL)
  4. washThe organic layer was washed with water (80 mL) and brine (80 mL)
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. customthe solvent was evaporated under reduced pressure
  8. customThe resulting residue was purified by silica gel column chromatography (ethyl acetate:hexane=1:2→1:1→2:1→1:0→chloroform:methanol=9:1)

Sources & evidence

ORD record
ord-a0544de46815493bbe93b228dcc315f3
Source dataset
uspto-grants-2013_12
Patent number
US08618094B2

Reaction notes

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