tert-Butanol → Methyl{1-[4-(trifluoromethyl)benzyl]-5-[4-(trifluoromethyl)phenyl]pyrrolidin-3-yl}acetate

HRID 1869766Notes

Reaction equation

HRID 1869766 reaction equation
[F:1][C:2]([F:30])([F:29])[C:3]1[CH:28]=[CH:27][C:6]([CH2:7][NH:8][CH:9]([C:17]2[CH:22]=[CH:21][C:20]([C:23]([F:26])([F:25])[F:24])=[CH:19][CH:18]=2)[CH2:10]/[CH:11]=[CH:12]/[C:13]([O:15][CH3:16])=[O:14])=[CH:5][CH:4]=1.N1C2C=CC=C(CO)[C:34]=2N=N1.C(O)(C)(C)C.[I-].[I-].[Sm+2]>C1C=CC=CC=1>[CH3:16][O:15][C:13](=[O:14])[CH2:12][CH:11]1[CH2:10][CH:9]([C:17]2[CH:18]=[CH:19][C:20]([C:23]([F:25])([F:24])[F:26])=[CH:21][CH:22]=2)[N:8]([CH2:7][C:6]2[CH:27]=[CH:28][C:3]([C:2]([F:29])([F:30])[F:1])=[CH:4][CH:5]=2)[CH2:34]1

Participants

6

Reactant 4

HCID 6386tert-ButanolHCID 57987371Methyl(2E)-5-{[4-(trifluoromethyl)benzyl]amino}-5-[4-(trifluoromethyl)phenyl]pent-2-enoateHCID 178506586HCID 178506586, compoundHCID 178519450HCID 178519450, compound

Product 1

HCID 76697410Methyl{1-[4-(trifluoromethyl)benzyl]-5-[4-(trifluoromethyl)phenyl]pyrrolidin-3-yl}acetate

Reagents, catalysts & solvents 1

HCID 241BenzeneSolvent

Conditions

Temperature
-78 °C

Procedure

The amine from Step 4 (400 mg, 0.9 mmol) was dissolved in benzene and benzotriazolemethanol (135 mg, 0.9 mmol) was added followed by powdered molecular sieves (470 mg). This was stirred overnight, the molecular sieves removed by filtration through Celite and the filtrate concentrated in vacuo. The residue was dissolved in THF (25 mL) and anhydrous t-butanol (0.17 mL, 0.9 mmol) was added. This solution was added dropwise via cannula onto a solution of samarium diiodide (27 mL, 2.7 mmol, 0.1M in THF) which was pre-cooled to −78° C. The mixture was stirred (−78° C. 0° C.) overnight then quenched with aq. K2CO3 and extracted with ethyl acetate. The organic extracts were washed with water, dried (MgSO4) and evaporated. The residue was purified on silica using 30-50% CH2Cl2 in iso-hexane to elute isomer a (245 mg) and isomer b (100 mg).

Workup

  1. customthe molecular sieves removed by filtration through Celite
  2. concentrationthe filtrate concentrated in vacuo
  3. dissolutionThe residue was dissolved in THF (25 mL)
  4. stirringThe mixture was stirred (−78° C. 0° C.) overnight
  5. customthen quenched with aq. K2CO3
  6. extractionextracted with ethyl acetate
  7. washThe organic extracts were washed with water
  8. dry with materialdried (MgSO4)
  9. customevaporated
  10. customThe residue was purified on silica using 30-50% CH2Cl2 in iso-hexane
  11. washto elute isomer a (245 mg) and isomer b (100 mg)

Sources & evidence

ORD record
ord-e229d0757839427fa5623eceef026e93
Source dataset
uspto-grants-2009_12
Patent number
US07638629B2

Reaction notes

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