2-Bromo-1,4-difluorobenzene → Tert-butyl 4-[(2,5-difluorophenyl)(hydroxy)methyl]piperidine-1-carboxylate

HRID 1373363

Reaktionsgleichung

Reaktionsgleichung von HRID 1373363
[F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1Br.C([Li])CCC.[C:15]([O:19][C:20]([N:22]1[CH2:27][CH2:26][CH:25]([CH:28]=[O:29])[CH2:24][CH2:23]1)=[O:21])([CH3:18])([CH3:17])[CH3:16]>O1CCCC1>[F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[CH:28]([OH:29])[CH:25]1[CH2:26][CH2:27][N:22]([C:20]([O:19][C:15]([CH3:17])([CH3:16])[CH3:18])=[O:21])[CH2:23][CH2:24]1

Komponenten

5

Edukt 3

HCID 678622-Bromo-1,4-difluorobenzeneHCID 1514430tert-Butyl 4-formylpiperidine-1-carboxylateHCID 178418339Butyllithium

Produkt 1

HCID 69344572Tert-butyl 4-[(2,5-difluorophenyl)(hydroxy)methyl]piperidine-1-carboxylateAusbeute 34 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel2×

Versuchsvorschrift

To a solution of 2,5-difluoro-1-bromobenzene (24.5 g, 127 mmol) in anhydrous tetrahydrofuran (400 ml) at −78° C. was added n-butyllithium (1.6M, 80 ml, 128 mmol). The solution was stirred for 15 minutes tert-butyl-4-formyl-piperidine-1-carboxylate (27.0 g, 127 mmol) added slowly in THF (50 ml). The mixture was allowed to warm to room temperature and stirred for 16 hours, quenched with water (200 ml) and extracted with ethyl acetate (3×150 ml). The combined organics were washed with water (50 ml), dried (MgSO4) and concentrated. The residue was purified by flash chromatography eluting with 3 to 10% ethyl acetate in iso hexanes to yield (RS)-tertbutyl 4-[(2,5-difluorophenyl)-hydroxymethyl]-piperidine-1-carboxylate as a colourless oil (14 g, 34%).

Aufarbeitung

  1. customquenched with water (200 ml)
  2. extractionextracted with ethyl acetate (3×150 ml)
  3. washThe combined organics were washed with water (50 ml)
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated
  6. customThe residue was purified by flash chromatography
  7. washeluting with 3 to 10% ethyl acetate in iso hexanes

Quellen und Nachweise

ORD-Eintrag
ord-203eaa1b5f8c4c2393b62ec513ff30f7
Quelldatensatz
uspto-grants-2007_01
Patentnummer
US07161006B2

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