Trifluoroacetic acid → HCID 58641163, Verbindung

HRID 1394944Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1394944
[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

Komponenten

8

Edukt 5

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

Produkt 1

HCID 58641163HCID 58641163, Verbindung

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6344DichloromethaneLösungsmittelHCID 6386tert-ButanolLösungsmittel

Versuchsvorschrift

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.

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-130517857dbe4011a893b9cc7da5662d
Quelldatensatz
uspto-grants-2008_03
Patentnummer
US07348440B2

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