Dichloromethane → HCID 66813551, compound

HRID 2264841Notes

Reaction equation

HRID 2264841 reaction equation
[NH2:1][C:2]([C@H:4]1[CH2:8][CH2:7][C@@H:6]([C:9]2[CH:14]=[CH:13][C:12]([O:15][CH2:16][C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=3[F:23])=[CH:11][CH:10]=2)[N:5]1C(OC(C)(C)C)=O)=[O:3].C(O)(C(F)(F)F)=O.C(Cl)[Cl:39]>>[ClH:39].[F:23][C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][C:17]=1[CH2:16][O:15][C:12]1[CH:13]=[CH:14][C:9]([C@@H:6]2[NH:5][C@@H:4]([C:2]([NH2:1])=[O:3])[CH2:8][CH2:7]2)=[CH:10][CH:11]=1

Participants

4

Reactant 3

HCID 6344DichloromethaneHCID 6422Trifluoroacetic acidHCID 59164847HCID 59164847, compound

Product 1

HCID 66813551HCID 66813551, compoundYield 92%

Procedure

To a solution of 1,1-dimethylethyl (2R,5S)-2-(aminocarbonyl)-5-(4-{[(2-fluorophenyl)methyl]oxy}phenyl)-1-pyrrolidinecarboxylate (D40, 145 mg, 0.37 mmol) in DCM (6 ml) was added TFA (1.5 ml) dropwise at 0° C. The mixture was stirred for 1 h under these conditions. After evaporating the solvent, the resulting crude material was purified by SCX cartridge, to afford the title compound (100 mg, 92%) as a mixture of diastereoisomers. The diastereoisomers were separated via chiral semipreparative HPLC: Column: chiralpak AD-H; Mobile phase: n-Hexane:Ethanol=70/30; Flow rate: 13 ml/min; UV wavelength range: 225 nm; Analysis time: 25 min. Analytical chromatographic conditions: Chiral HPLC: Column: chiralpak AD-H 5 um, 250×4.6 mm; Mobile phase: A: n-Hexane; B: Ethanol; Gradient: isocratic 30% B; Flow rate: 0.8 ml/min; UV wavelength range: 200-400 nm; Analysis time: 30 min; Rt: 14.02 min (E21); Rt: 16.12 min (E20)

Workup

  1. customAfter evaporating the solvent
  2. customthe resulting crude material was purified by SCX cartridge

Sources & evidence

ORD record
ord-7ec7ab33ec2f4aaa95b2f069d2efde28
Source dataset
uspto-grants-2010_12
Patent number
US07855218B2

Reaction notes

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