(Diethylamino)sulfur trifluoride → 4-Fluoro-4-[4-[[(phenylmethoxy)carbonyl]amino]-2-fluorophenyl]-1-piperidinecarboxylic acid phenylmethyl ester

HRID 428766

Reaktionsgleichung

Reaktionsgleichung von HRID 428766
C(N(S(F)(F)[F:7])CC)C.[C:10]1([CH2:16][O:17][C:18]([N:20]2[CH2:25][CH2:24][C:23](O)([C:26]3[CH:31]=[CH:30][C:29]([NH:32][C:33]([O:35][CH2:36][C:37]4[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=4)=[O:34])=[CH:28][C:27]=3[F:43])[CH2:22][CH2:21]2)=[O:19])[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.C(=O)(O)[O-].[Na+]>C(Cl)Cl.O>[C:10]1([CH2:16][O:17][C:18]([N:20]2[CH2:25][CH2:24][C:23]([F:7])([C:26]3[CH:31]=[CH:30][C:29]([NH:32][C:33]([O:35][CH2:36][C:37]4[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=4)=[O:34])=[CH:28][C:27]=3[F:43])[CH2:22][CH2:21]2)=[O:19])[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1

Komponenten

6

Edukt 3

HCID 123472(Diethylamino)sulfur trifluorideHCID 516892Sodium BicarbonateHCID 542846344-Hydroxy-4-[2-fluoro-4-[[(phenylmethoxy)carbonyl]amino]phenyl]-1-piperidinecarboxylic acid phenylmethyl ester

Produkt 1

HCID 538510694-Fluoro-4-[4-[[(phenylmethoxy)carbonyl]amino]-2-fluorophenyl]-1-piperidinecarboxylic acid phenylmethyl ester

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 6344DichloromethaneLösungsmittel2×

Reaktionsbedingungen

Temperatur
-78 °C

Versuchsvorschrift

To a solution of diethylaminosulfur trifluoride (DAST, 0.65 mL) in dry methylene chloride (49 mL) at −78° C. under N2 is added a solution of 4-hydroxy-4-[4-[[(phenylmethoxy)carbonyl]amino]-2-fluorophenyl]-1piperidinecarboxylic acid phenylmethyl ester (EXAMPLE 74, Step 1, 2.25 g) in dry methylene chloride (47 mL) over 2 mins. The resulting mixture is stirred at −78° C. for 1 hr and at ambient temperature for 30 mins and is then adjusted to ph 8 with saturated aqueous sodium bicarbonate (50 mL), diluted with water (50 mL), and the layers are separated. The organic phase is washed with water (25 mL) and saline (25 mL), dried over anhydrous sodium sulfate and concentrated under reduced pressure, and the residue is chromatographed on silica gel (230-400 mesh, 150 g) eluting with methanol/methylene chloride (0.5/99.5). Those fractions with an R7=0.27 by TLC (ethyl acetate/hexane, 25/75) are pooled and concentrated to give the title compound (contaminated with approx. 15% of the elimination side product). An analytical sample is prepared by radial chromatography (100 μ silica gel rotor, ethyl acetate/hexane (20/80) eluent), mp 116-118° C.

Aufarbeitung

  1. customthe layers are separated
  2. washThe organic phase is washed with water (25 mL) and saline (25 mL)
  3. dry with materialdried over anhydrous sodium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customthe residue is chromatographed on silica gel (230-400 mesh, 150 g)
  6. washeluting with methanol/methylene chloride (0.5/99.5)
  7. concentrationconcentrated

Quellen und Nachweise

ORD-Eintrag
ord-1373bdb964c54b9dadcb35b3a5101d8f
Quelldatensatz
uspto-grants-2001_11
Patentnummer
US06313307B1

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