Benzaldehyde → (3S,4R)-3-benzylaminomethyl-1-benzyloxycarbonyl-4-fluoropyrrolidine

HRID 2108793Notes

Reaction equation

HRID 2108793 reaction equation
[NH2:1][CH2:2][C@@H:3]1[C@@H:7]([F:8])[CH2:6][N:5]([C:9]([O:11][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[O:10])[CH2:4]1.NCC1CN(C(O[CH2:29][C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)=O)CC=1.C(=O)C1C=CC=CC=1.Cl.[OH-].[Na+]>CO>[CH2:29]([NH:1][CH2:2][C@@H:3]1[C@@H:7]([F:8])[CH2:6][N:5]([C:9]([O:11][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[O:10])[CH2:4]1)[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1

Participants

7

Reactant 5

HCID 240BenzaldehydeHCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 230620723-Aminomethyl-1-benzyloxycarbonyl-3-pyrrolineHCID 66705221(3S,4R)-3-aminomethyl-1-benzyloxycarbonyl-4-fluoropyrrolidine

Product 1

HCID 66704865(3S,4R)-3-benzylaminomethyl-1-benzyloxycarbonyl-4-fluoropyrrolidine

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

The mixture (310 mg) of (3S,4R)-3-aminomethyl-1-benzyloxycarbonyl-4-fluoropyrrolidine and 3-aminomethyl-1-benzyloxycarbonyl-3-pyrroline was dissolved in methanol (4 mL). To this solution, molecular sieves 4A (130 mg) and then benzaldehyde (0.13 mL) were added and the mixture was stirred at room temperature for 1 hour. Subsequently, a borane/pyridine complex (0.19 mL) was added and the reaction mixture was further stirred at room temperature for 4 hours. 6 mol/L hydrochloric acid (2 mL) was then added and the mixture was stirred at room temperature for 1 hour, followed by addition of a 30% aqueous solution of sodium hydroxide to make the mixture basic. The mixture was then extracted with diethyl ether (3×10 mL). The diethyl ether layers were combined and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (eluant: dichloromethane: methanol=10:1) to give (3S,4R)-3-benzylaminomethyl-1-benzyloxycarbonyl-4-fluoropyrrolidine as a pale yellow oil (177 mg).

Workup

  1. additionSubsequently, a borane/pyridine complex (0.19 mL) was added
  2. stirringthe reaction mixture was further stirred at room temperature for 4 hours
  3. stirringthe mixture was stirred at room temperature for 1 hour
  4. extractionThe mixture was then extracted with diethyl ether (3×10 mL)
  5. concentrationconcentrated under reduced pressure
  6. customThe resulting residue was purified by silica gel column chromatography (eluant: dichloromethane: methanol=10:1)

Sources & evidence

ORD record
ord-b2c624ef71e043b799ccf8a268e9696a
Source dataset
uspto-grants-2009_04
Patent number
US07514451B2

Reaction notes

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