Trifluoroacetic acid → HCID 58641163, compound

HRID 1394944Notes

Reaction equation

HRID 1394944 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(OC(C)(C)C)=O)[C@H:11]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH:10]=1.F[C:28](F)(F)[C:29]([OH:31])=[O:30].BrCC(OCC)=O.C(N(CC)C(C)C)(C)C.[OH-].[Na+]>C(O)(C)(C)C.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]([CH2:28][C:29]([OH:31])=[O:30])[C@H:11]([C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=2)[CH:10]=1

Participants

8

Reactant 5

HCID 6422Trifluoroacetic acidHCID 7748Ethyl bromoacetateHCID 14798Sodium HydroxideHCID 81531DiisopropylethylamineHCID 58641236HCID 58641236, compound

Product 1

HCID 58641163HCID 58641163, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 6386tert-ButanolSolvent

Procedure

A solution of tert-butyl(2S)-4-(2,5-difluorophenyl)-2-phenyl-2,5-dihydro-1H-pyrrole-1-carboxylate (5-5, 50 mg, 0.14 mmol, 1 equiv) in a 1:1 mixture of dichloromethane and trifluoroacetic acid (10 mL) was stirred for 30 minutes, then concentrated. The residue was partitioned between aqueous saturated sodium bicarbonate solution (60 mL) and ethyl acetate (50 mL). The organic layer was dried over sodium sulfate and concentrated. A solution of the residue, ethyl bromoacetate (16 μL, 0.14 mmol, 1.0 equiv) and N,N-diisopropylethylamine (29 μL, 0.17 mmol, 1.2 equiv) in DMP (5 mL) was heated at 70° C. for 3 hours. The reaction mixture was partitioned between water (125 mL) and ethyl acetate (2×100 mL). The combined organic layers were dried over sodium sulfate and concentrated. A solution of the residue and sodium hydroxide (1N, 280 μL, 0.28 mmol, 2.0 equiv) in tert-butanol (10 mL) was heated at 45° C. for 20 hours. The reaction mixture was then partitioned between water and ethyl ether. The aqueous layer was acidified to pH 4 with aqueous HCl solution, then extracted with ethyl acetate (2×40 mL). The combined organic layers were dried over sodium sulfate and concentrated to provide [(2S)-4-(2,5-difluorophenyl)-2-phenyl-2,5-dihydro-1H-pyrrol-1-yl]acetic acid (28-1) as a colorless oil. LRMS m/z (M+H) 316.3 found, 316.1 required.

Workup

  1. concentrationconcentrated
  2. customThe residue was partitioned between aqueous saturated sodium bicarbonate solution (60 mL) and ethyl acetate (50 mL)
  3. dry with materialThe organic layer was dried over sodium sulfate
  4. concentrationconcentrated
  5. customThe reaction mixture was partitioned between water (125 mL) and ethyl acetate (2×100 mL)
  6. dry with materialThe combined organic layers were dried over sodium sulfate
  7. concentrationconcentrated
  8. customThe reaction mixture was then partitioned between water and ethyl ether
  9. extractionextracted with ethyl acetate (2×40 mL)
  10. dry with materialThe combined organic layers were dried over sodium sulfate
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-130517857dbe4011a893b9cc7da5662d
Source dataset
uspto-grants-2008_03
Patent number
US07348440B2

Reaction notes

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