Trifluoroacetic acid → HCID 59468963, compound

HRID 1690107Notes

Reaction equation

HRID 1690107 reaction equation
[C:1]([CH2:3][CH2:4][C@@:5]1([C:31]([O:33]C)=O)[CH2:9][CH2:8][C@H:7]([C:10]2[CH:15]=[CH:14][C:13]([O:16]CC3C=CC=CC=3)=[CH:12][CH:11]=2)[N:6]1C(OC(C)(C)C)=O)#[N:2].C(O)(C(F)(F)F)=O>CO.[Ni].ClCCl>[OH:16][C:13]1[CH:14]=[CH:15][C:10]([CH:7]2[CH2:8][CH2:9][C@:5]3([CH2:4][CH2:3][CH2:1][NH:2][C:31]3=[O:33])[NH:6]2)=[CH:11][CH:12]=1

Participants

6

Reactant 2

HCID 6422Trifluoroacetic acidHCID 59468941HCID 59468941, compound

Product 1

HCID 59468963HCID 59468963, compoundYield 19.4%

Reagents, catalysts & solvents 3

HCID 935NickelCatalystHCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 1-(1,1-dimethylethyl) 2-methyl (2R,5R)-2-(2-cyanoethyl)-5-{4-[(phenylmethyl)oxy]phenyl}-1,2-pyrrolidinedicarboxylate (D49, 215 mg, 0.46 mmol) in methanol (20 mL) was added Raney Nickel (slurry in water, 1 spatula) and the mixture was stirred under a hydrogen atmosphere (6 atm) for 4.5 hours. The catalyst was filtered off, the solvent removed under reduced pressure, and the residue treated with toluene (3×20 mL) and dried under vacuum. The crude oil obtained was dissolved in dichloromethane and the resulting solution cooled to 0° C. and TFA (0.2 mL) was added dropwise. After 1 h at room temperature the solvent was removed under vacuum and the residue purified by SCX column and by chromatography on silica gel using dichloromethane/methanol (95:5) to afford the title compound (22 mg, 19%) as a 66/33 mixture of epimers at the benzylic position. Rt (HPLC) 2.16 min; MS: (ES/+) m/z: 247 [MH+]; C14H18N2O2 requires 246.

Workup

  1. filtrationThe catalyst was filtered off
  2. customthe solvent removed under reduced pressure
  3. additionthe residue treated with toluene (3×20 mL)
  4. customdried under vacuum
  5. customThe crude oil obtained
  6. customAfter 1 h at room temperature the solvent was removed under vacuum
  7. customthe residue purified by SCX column and by chromatography on silica gel

Sources & evidence

ORD record
ord-0985723fb95b4852b7f5f453d08abbfe
Source dataset
uspto-grants-2012_04
Patent number
US08153623B2

Reaction notes

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