Potassium tert-butoxide → tert-Butyl 2,2-difluoro-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecane-9-carboxylate

HRID 1689280Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1689280
Br[C:2]([F:22])([F:21])[C:3]([NH:5][CH2:6][C:7]1([OH:20])[CH2:12][CH2:11][N:10]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:9][CH2:8]1)=[O:4].CC(C)([O-])C.[K+]>C1COCC1>[F:21][C:2]1([F:22])[C:3](=[O:4])[NH:5][CH2:6][C:7]2([CH2:12][CH2:11][N:10]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:9][CH2:8]2)[O:20]1

Komponenten

4

Edukt 2

HCID 23665647Potassium tert-butoxideHCID 57988980tert-Butyl 4-((2-bromo-2,2-difluoroacetamido)methyl)-4-hydroxypiperidine-1-carboxylate

Produkt 1

HCID 57989103tert-Butyl 2,2-difluoro-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecane-9-carboxylate

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel2×

Versuchsvorschrift

A solution of tert-butyl 4-((2-bromo-2,2-difluoroacetamido)methyl)-4-hydroxypiperidine-1-carboxylate (example 37, step a) (3.2 g) in THF (40 mL) was added dropwise over 15 minutes to a stirred solution of potassium tert-butoxide (1M in t-butanol, 16.53 mL) and THF (60 mL) at 70° C. under nitrogen. At the end of the addition the mixture was heated for a further 10 minutes and then cooled to room temperature. The mixture was partitioned between ethyl acetate and brine, the organic layer was dried over sodium sulphate, filtered and the solvent evaporated under reduced pressure. The crude product was purified by flash silica chromatography using 30% isohexane in ethyl acetate. Pure fractions were evaporated to dryness to afford the subtitled compound. Yield 0.55 g.

Aufarbeitung

  1. additionAt the end of the addition the mixture
  2. temperaturewas heated for a further 10 minutes
  3. customThe mixture was partitioned between ethyl acetate and brine
  4. dry with materialthe organic layer was dried over sodium sulphate
  5. filtrationfiltered
  6. customthe solvent evaporated under reduced pressure
  7. customThe crude product was purified by flash silica chromatography
  8. customPure fractions were evaporated to dryness

Quellen und Nachweise

ORD-Eintrag
ord-3616cf9c84d8421e9c69c1e5a0fc4fd5
Quelldatensatz
uspto-grants-2012_04
Patentnummer
US08148373B2

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