3-Chloroaniline → HCID 66774596, compound

HRID 1644810Notes

Reaction equation

HRID 1644810 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][C:11]([F:14])([F:13])[CH2:10][C@H:9]1[CH:15]=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Cl:17][C:18]1[CH:19]=[C:20]([CH:22]=[CH:23][CH:24]=1)[NH2:21].[BH4-].[Na+]>CC(C)[O-].CC(C)[O-].CC(C)[O-].CC(C)[O-].[Ti+4].CO>[C:1]([O:5][C:6]([N:8]1[CH2:12][C:11]([F:14])([F:13])[CH2:10][C@H:9]1[CH2:15][NH:21][C:20]1[CH:22]=[CH:23][CH:24]=[C:18]([Cl:17])[CH:19]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 3

HCID 79323-ChloroanilineHCID 4311764Sodium borohydrideHCID 866356221,1-Dimethylethyl (2S)-4,4-difluoro-2-formyl-1-pyrrolidinecarboxylate

Product 1

HCID 66774596HCID 66774596, compoundYield 12%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 11026Titanium isopropoxideSolvent

Procedure

Solution of (S)-4,4-difluoro-2-formyl-pyrrolidine-1-carboxylic acid tert-butyl ester (1 g, 0.0042 mol) and 3-chloroaniline (0.53 mL, 0.0042 mol) in titanium tetraisopropoxide (5 mL) was allowed to stir for 12 h. The reaction was monitored by TLC. After disappearance of starting reaction on TLC, the mixture was diluted with methanol (20 mL) followed by the addition of sodium borohydride (0.33 g, 0.0084 mol) in portions. The reaction mixture was stirred for 6 h. The reaction was quenched with water and extracted with DCM (3×50 mL). The organic layer was dried over anhydrous Na2SO4 and the volatiles were removed using a rotary evaporator to give a crude oil, which was then purified via column chromatography (5% methanol: DCM, mesh Size—100-200 silica, diameter of column—2.5 cm, height of silica—approx. 4 inch) to afford the desired (S)-2-[(3-chloro-phenylamino)-methyl]-4,4-difluoro-pyrrolidine-1-carboxylic acid tert-butyl ester as a sticky solid (0.15 g, 12%).

Workup

  1. customreaction on TLC
  2. stirringThe reaction mixture was stirred for 6 h
  3. customThe reaction was quenched with water
  4. extractionextracted with DCM (3×50 mL)
  5. dry with materialThe organic layer was dried over anhydrous Na2SO4
  6. customthe volatiles were removed
  7. customa rotary evaporator
  8. customto give a crude oil, which
  9. customwas then purified via column chromatography (5% methanol

Sources & evidence

ORD record
ord-ca58ea44ad44491c918b1f93ba753e6b
Source dataset
uspto-grants-2012_02
Patent number
US08124636B2

Reaction notes

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