rac-(3R,4S)-1-Benzyl-3-(4-fluoro-phenyl)-4-nitro-pyrrolidine → 1-Benzyl-4-(4-fluorophenyl)pyrrolidin-3-amine

HRID 1365910Notes

Reaction equation

HRID 1365910 reaction equation
[CH2:1]([N:8]1[CH2:12][CH:11]([N+:13]([O-])=O)[CH:10]([C:16]2[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=2)[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1>C1COCC1.CCOCC.[Ti](Cl)(Cl)(Cl)Cl.[Zn]>[CH2:1]([N:8]1[CH2:9][CH:10]([C:16]2[CH:17]=[CH:18][C:19]([F:22])=[CH:20][CH:21]=2)[CH:11]([NH2:13])[CH2:12]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 1

HCID 66940721rac-(3R,4S)-1-Benzyl-3-(4-fluoro-phenyl)-4-nitro-pyrrolidine

Product 1

HCID 669409261-Benzyl-4-(4-fluorophenyl)pyrrolidin-3-amineYield 22.6%

Reagents, catalysts & solvents 4

HCID 23994ZincCatalystHCID 24193Titanium TetrachlorideCatalystHCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
68 °C

Procedure

Titanium (IV) chloride (179.4 g, 0.94 mol) was added drop wise to a suspension of zinc powder (123.6 g, 1.89 mol) in THF (1200 ml). This solution was heated at 68° C. for one hour, then cooled to RT before rac-(3R,4S)-1-benzyl-3-(4-fluoro-phenyl)-4-nitro-pyrrolidine (94 g, 0.31 mol) in THF (400 ml) was added. The reaction mixture was then stirred at reflux over night. The reaction was cooled to RT, diluted with 3000 ml of Et2O, washed with an aqueous solution of NaHCO3 and the organic phases were dried over Na2SO4. Flash chromatography (SiO2, CH2Cl2/MeOH, 9:1) yielded 18.9 g (22%) of rac-(3S,4R)-1-benzyl-4-(4-fluoro-phenyl)-pyrrolidin-3-ylamine as a brown oil.

Workup

  1. additionwas added
  2. temperatureat reflux over night
  3. temperatureThe reaction was cooled to RT
  4. washwashed with an aqueous solution of NaHCO3
  5. dry with materialthe organic phases were dried over Na2SO4

Sources & evidence

ORD record
ord-9582d1c795d94db5a74cf860bac88832
Source dataset
uspto-grants-2011_02
Patent number
US07893062B2

Reaction notes

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