Trifluoroacetic acid → 2-Amino-3-[(3R,4S)-3-({(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl}oxy)-4-phenylpyrrolidin-1-yl]-3-oxopropan-1-ol

HRID 2377037Notes

Reaction equation

HRID 2377037 reaction equation
[F:1][C:2]([F:44])([F:43])[C:3]1[CH:4]=[C:5]([C@H:13]([O:15][C@@H:16]2[C@@H:20]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[CH2:19][N:18]([C:27]([CH:29]3[CH2:33][O:32]C(C)(C)[N:30]3C(OC(C)(C)C)=O)=[O:28])[CH2:17]2)[CH3:14])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.C1(OC)C=CC=CC=1.C(O)(C(F)(F)F)=O>C(Cl)Cl>[NH2:30][CH:29]([C:27]([N:18]1[CH2:19][C@H:20]([C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=2)[C@@H:16]([O:15][C@@H:13]([C:5]2[CH:6]=[C:7]([C:9]([F:10])([F:11])[F:12])[CH:8]=[C:3]([C:2]([F:44])([F:1])[F:43])[CH:4]=2)[CH3:14])[CH2:17]1)=[O:28])[CH2:33][OH:32]

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 7519AnisoleHCID 11433611tert-Butyl 4-{[(3R,4S)-3-({(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl}oxy)-4-phenylpyrrolidin-1-yl]carbonyl}-2,2-dimethyl-1,3-oxazolidine-3-carboxylate

Product 1

HCID 112717972-Amino-3-[(3R,4S)-3-({(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl}oxy)-4-phenylpyrrolidin-1-yl]-3-oxopropan-1-ol

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 48 mg tert-butyl 4-{[(3R,4S)-3-({(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl}oxy)-4-phenylpyrrolidin-1-yl]carbonyl}-2,2-dimethyl-1,3-oxazolidine-3-carboxylate (Example 4) in 3 mL methylene chloride was added 0.5 mL anisole and 3 mL TFA. The reaction mixture was stirred at RT for 2 hr and then the volatiles were removed under vacuum. The residue was partitioned between methylene chloride (5 mL) and sat. aq. sodium carbonate (5 mL). The organic layer was dried over sodium sulfate, filtered and the solvent removed under vacuum. The residue was purified by prep TLC eluting with methylene chloride/methanol (9/1) to afford the title compound. 1H-NMR (CDCl3): δ: 1.43 (d, 3H, 6.5 Hz), 2.0 (br. s, 3H), 3.30-4.18 (m, 9H), 4.54 (m, 1H), 7.00-7.08 (m, 2H), 7.22-7.31 (m, 3H), 7.56 (s, 2H), 7.75 (s, 1H)ppm. MS: 491.2 (MH+) observed.

Workup

  1. customthe volatiles were removed under vacuum
  2. customThe residue was partitioned between methylene chloride (5 mL) and sat. aq. sodium carbonate (5 mL)
  3. dry with materialThe organic layer was dried over sodium sulfate
  4. filtrationfiltered
  5. customthe solvent removed under vacuum
  6. customThe residue was purified by prep TLC
  7. washeluting with methylene chloride/methanol (9/1)

Sources & evidence

ORD record
ord-8d52966cafd049edb5f1ee3c5bebacf6
Source dataset
uspto-grants-2008_12
Patent number
US07468437B2

Reaction notes

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