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

HRID 859890Notes

Reaction equation

HRID 859890 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.[CH:19](=O)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.Cl.[OH-].[Na+]>CO>[CH2:19]([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:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1

Participants

6

Reactant 4

HCID 240BenzaldehydeHCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 66704920benzyl (3S,4S)-3-(aminomethyl)-4-fluoropyrrolidine-1-carboxylate

Product 1

HCID 66704898(3S,4S)-3-benzylaminomethyl-1-benzyloxycarbonyl-4-fluoropyrrolidine

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

(3S,4S)-3-Aminomethyl-1-benzyloxycarbonyl-4-fluoropyrrolidine (1.10 g) was dissolved in methanol (13 mL). To this solution, molecular sieves 4A (440 mg) and benzaldehyde (0.44 mL) were sequentially added and the mixture was stirred at room temperature for 1 hour. Subsequently, a borane-pyridine complex (0.44 mL) was added and the mixture was further stirred at room temperature for 3.5 hours. This was followed by addition of 6 mol/L hydrochloric acid (7.3 mL) and stirring at room temperature for 1 hour. Subsequently, a 30% aqueous solution of sodium hydroxide was added to make the mixture basic and the mixture was extracted with diethyl ether (2×100 mL). The diethyl ether extracts were combined and the combined diethyl ether layer was dried over anhydrous sodium sulfate and was then concentrated under reduced pressure. The resulting residue was purified on a silica gel column (eluant=hexane:ethyl acetate=4:1 shifted to 1:1) to give 1.18 g of (3S,4S)-3-benzylaminomethyl-1-benzyloxycarbonyl-4-fluoropyrrolidine as a colorless tar-like product.

Workup

  1. additionSubsequently, a borane-pyridine complex (0.44 mL) was added
  2. stirringthe mixture was further stirred at room temperature for 3.5 hours
  3. stirringstirring at room temperature for 1 hour
  4. extractionthe mixture was extracted with diethyl ether (2×100 mL)
  5. dry with materialthe combined diethyl ether layer was dried over anhydrous sodium sulfate
  6. concentrationwas then concentrated under reduced pressure
  7. customThe resulting residue was purified on a silica gel column (eluant=hexane:ethyl acetate=4:1 shifted to 1:1)

Sources & evidence

ORD record
ord-e984cd2df16d4a1bb05cab7d40713f74
Source dataset
uspto-grants-2006_12
Patent number
US07153851B2

Reaction notes

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