Triethylamine → 4,4-Difluorocyclohexanecarboxylic acid

HRID 1644245Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1644245
O=CC[C@H](N[C:12]([CH:14]1[CH2:19][CH2:18][C:17]([F:21])([F:20])[CH2:16][CH2:15]1)=[O:13])C1C=CC=CC=1.C(O[BH-](OC(=O)C)OC(=O)C)(=[O:24])C.[Na+].C(N(CC)CC)C>ClCCCl>[F:20][C:17]1([F:21])[CH2:18][CH2:19][CH:14]([C:12]([OH:13])=[O:24])[CH2:15][CH2:16]1

Komponenten

5

Edukt 3

HCID 8471TriethylamineHCID 5049666Sodium triacetoxyborohydrideHCID 98792204,4-Difluoro-N-[(1S)-3-oxo-1-phenylpropyl]cyclohexanecarboxamide

Produkt 1

HCID 27791364,4-Difluorocyclohexanecarboxylic acidAusbeute 148,1 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 111,2-DichloroethaneLösungsmittel

Versuchsvorschrift

To 21.1 mg (0.072 mmol) of 1-methyl-3-(tetrahydropyran-4-ylmethyl)-bicyclo[3.2.1]-1β,3,8-triaza-spiro[4.5]dodecan-2-one in 1.5 mL of DCE was added 21.2 mg (0.072 mmol, 1 eq.) of 4,4-difluoro-cyclohexanecarboxylic acid ((S)-3-oxo-1-phenyl-propyl)-amide, 19 mg (0.09 mmol, 1.25 eq.) of sodium triacetoxyborohydride and 12 μL (0.086 mmol, 1.2 eq.) of triethylamine. The reaction mixture was stirred overnight at room temperature and concentrated in vacuo. The crude was purified by flash chromatography on silica gel (DCM/MeOH: 0 to 100) and redissolved in 1 mL of methanol and 100 μL of HCl (1N). The solution was then concentrated in vacuo and diluted with 2 mL of water to give after lyophilization 17.5 mg (40%) of 4,4-difluoro-cyclohexanecarboxylic acid {(S)-3-[1-methyl-3-(tetrahydropyran-4-ylmethyl)-bicyclo[3.2.1]-2-oxo-1β,3,8-triaza-spiro[4.5]dodec-8-yl]-1-phenyl-propyl}-amide hydrochloride.

Aufarbeitung

  1. concentrationconcentrated in vacuo
  2. customThe crude was purified by flash chromatography on silica gel (DCM/MeOH: 0 to 100)
  3. dissolutionredissolved in 1 mL of methanol
  4. concentrationThe solution was then concentrated in vacuo
  5. additiondiluted with 2 mL of water

Quellen und Nachweise

ORD-Eintrag
ord-0fa43a03e25345d1aaf532ea064bf06f
Quelldatensatz
uspto-grants-2012_02
Patentnummer
US08124613B2

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