4-(Trifluoromethyl)phenol → Rac-[5-methanesulfonyl-2-((s)-2,2,2-trifluoro-1-methyl-ethoxy)-phenyl]-[3-(4-trifluoromethyl-phenoxymethyl)-pyrrolidin-1-yl]-methanone

HRID 552688Notes

Reaction equation

HRID 552688 reaction equation
[OH:1][CH2:2][CH:3]1[CH2:7][CH2:6][N:5]([C:8]([C:10]2[CH:15]=[C:14]([S:16]([CH3:19])(=[O:18])=[O:17])[CH:13]=[CH:12][C:11]=2[O:20][C@@H:21]([CH3:26])[C:22]([F:25])([F:24])[F:23])=[O:9])[CH2:4]1.O[C:28]1[CH:33]=[CH:32][C:31]([C:34]([F:37])([F:36])[F:35])=[CH:30][CH:29]=1.C1(P(C2C=CC=CC=2)C2C=CC=CN=2)C=CC=CC=1.N(C(OC(C)(C)C)=O)=NC(OC(C)(C)C)=O>O1CCCC1.C(OCC)(=O)C>[CH3:19][S:16]([C:14]1[CH:13]=[CH:12][C:11]([O:20][C@@H:21]([CH3:26])[C:22]([F:24])([F:25])[F:23])=[C:10]([C:8]([N:5]2[CH2:6][CH2:7][CH:3]([CH2:2][O:1][C:28]3[CH:33]=[CH:32][C:31]([C:34]([F:37])([F:36])[F:35])=[CH:30][CH:29]=3)[CH2:4]2)=[O:9])[CH:15]=1)(=[O:17])=[O:18]

Participants

7

Reactant 4

HCID 678744-(Trifluoromethyl)phenolHCID 97268Di-tert-butyl azodicarboxylateHCID 6218932-PyridyldiphenylphosphineHCID 59030469Rac-(3-hydroxymethyl-pyrrolidin-1-yl)-[5-methanesulfonyl-2-((s)-2,2,2-trifluoro-1-methyl-ethoxy)-phenyl]-methanone

Product 1

HCID 59030456Rac-[5-methanesulfonyl-2-((s)-2,2,2-trifluoro-1-methyl-ethoxy)-phenyl]-[3-(4-trifluoromethyl-phenoxymethyl)-pyrrolidin-1-yl]-methanone

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of 70 mg rac-(3-Hydroxymethyl-pyrrolidin-1-yl)-[5-methanesulfonyl-2-((S)-2,2,2-trifluoro-1-methyl-ethoxy)-phenyl]-methanone (Example C1) in 1.4 ml tetrahydrofuran were added 30 mg 4-hydroxybenzotrifluoride and 50 mg diphenyl-2-pyridylphosphine. 43 mg Di-tert-butyl azodicarboxylate was added. The mixture was stirred at 70° C. for 23 hours. The solvent was removed in vacuo. The oil was purified on silica gel (eluent: ethyl acetate) to yield a yellow gum. The gum was dissolved in ethyl acetate. The solution was washed 3 times with HCl 5N, once with water, dried over Na2SO4, filtered and concentrated in vacuo to provide the title compound as a light yellow foam. MS (m/e): 540.3 (M+H+, 100%).

Workup

  1. customThe solvent was removed in vacuo
  2. customThe oil was purified on silica gel (eluent: ethyl acetate)
  3. customto yield a yellow gum
  4. washThe solution was washed 3 times with HCl 5N
  5. dry with materialonce with water, dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-65eb1d6bb9254bd2b1f1f32ac9968b90
Source dataset
uspto-grants-2011_05
Patent number
US07951836B2

Reaction notes

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