Trifluoroacetic acid → HCID 58641434, compound

HRID 1394937Notes

Reaction equation

HRID 1394937 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[C:9]1[CH2:13][N:12]([C:14](OC(C)(C)C)=[O:15])[C@H:11]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH:10]=1.FC(F)(F)C(O)=O.C(N(CC)CC)C.[OH:41][C@@H:42]([C:46]([CH3:49])([CH3:48])[CH3:47])C(O)=O.C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F>ClCCl>[F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[C:9]1[CH2:13][N:12]([C:14](=[O:15])[C@@H:42]([OH:41])[C:46]([CH3:49])([CH3:48])[CH3:47])[C@H:11]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH:10]=1

Participants

7

Reactant 5

HCID 6422Trifluoroacetic acidHCID 8471Triethylamine2×HCID 2724699PyBOP2×HCID 11097105(2S)-2-hydroxy-3,3-dimethylbutanoic acid2×HCID 58641236HCID 58641236, compound

Product 1

HCID 58641434HCID 58641434, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of tert-butyl(2S)-4-(2,5-difluorophenyl)-2-phenyl-2,5-dihydro-1H-pyrrole-1-carboxylate (5-5, 113 mg, 0.316 mmol, 1 equiv) in a 1:1 mixture of dichloromethane and trifluoroacetic acid (20 mL) was stirred for 30 minutes, then concentrated. The residue was dried via toluene azeotrope (1×10 mL), then dissolved in DMF (4 mL). Triethylamine (0.176 mL, 1.27 mmol, 4.00 equiv), (2S)-2-hydroxy-3,3-dimethylbutanoic acid (84 mg, 0.632 mmol, 2.00 equiv), and PYBOP (329 mg, 0.632 mmol, 2.00 equiv) were added, and the resulting mixture was stirred at 23° C. for 24 hours. Additional triethylamine (0.176 mL, 1.27 mmol, 4.00 equiv), (2S)-2-hydroxy-3,3-dimethylbutanoic acid (84 mg, 0.632 mmol, 2.00 equiv), and PYBOP (329 mg, 0.632 mmol, 2.00 equiv) were added, and the resulting mixture was stirred at 23° C. for 20 hours. The reaction mixture was partitioned between water (70 mL) and ethyl acetate (2×55 mL). The combined organic layers were dried over sodium sulfate and concentrated. The residue was purified by reverse-phase LC (H2O/CH3CN gradient w/0.1% TFA present) to provide (2S)-1-[(2S)-4-(2,5-difluorophenyl)-2-phenyl-2,5-dihydro-1H-pyrrol-1-yl]-3,3-dimethyl-1-oxobutan-2-ol (22-1) as a white solid. 1H NMR (500 MHz, CDCl3) rotamers: δ 7.43-7.02 (m, 8H), 6.42 (m, 1H), 5.93 (m, 1H), 5.01-4.82 (m, 2H), 4.16 (major rotamer, s, 1H), 3.85 (minor rotamer, s, 1H), 1.00 (minor, s, 9H), 0.92 (major, s, 9H). LRMS m/z (M+H) 372.0 found, 372.2 required.

Workup

  1. concentrationconcentrated
  2. dry with materialThe residue was dried via toluene
  3. dissolutiondissolved in DMF (4 mL)
  4. stirringthe resulting mixture was stirred at 23° C. for 24 hours
  5. stirringthe resulting mixture was stirred at 23° C. for 20 hours
  6. customThe reaction mixture was partitioned between water (70 mL) and ethyl acetate (2×55 mL)
  7. dry with materialThe combined organic layers were dried over sodium sulfate
  8. concentrationconcentrated
  9. customThe residue was purified by reverse-phase LC (H2O/CH3CN gradient w/0.1% TFA present)

Sources & evidence

ORD record
ord-7de177819a314a009defb74e7c88c61f
Source dataset
uspto-grants-2008_03
Patent number
US07348440B2

Reaction notes

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