Triethylamine → 2-{[(2S)-1'-{2-[(5R)-3-[3,5-Bis(trifluoromethyl)benzoyl]-5-(4-fluorophenyl)-1,3-oxazolidin-5-yl]ethyl}-2,3-dihydrospiro[indene-1,4'-piperidin]-2-yl]oxy}-N-(4-hydroxybutyl)-N-methylacetamide

HRID 446545Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 446545
[F:1][C:2]([F:49])([F:48])[C:3]1[CH:4]=[C:5]([CH:41]=[C:42]([C:44]([F:47])([F:46])[F:45])[CH:43]=1)[C:6]([N:8]1[CH2:12][C@@:11]([CH2:20][CH2:21][N:22]2[CH2:27][CH2:26][C:25]3([C:35]4[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=4)[CH2:29][C@@H:28]3[O:36][CH2:37][C:38](O)=[O:39])[CH2:24][CH2:23]2)([C:13]2[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=2)[O:10][CH2:9]1)=[O:7].C(N(CC)CC)C.C(Cl)(=O)C(C)(C)C.[CH3:64][NH:65][CH2:66][CH2:67][CH2:68][CH2:69][OH:70].C(=O)([O-])O.[Na+]>ClCCl.C(OCC)(=O)C>[F:49][C:2]([F:48])([F:1])[C:3]1[CH:4]=[C:5]([CH:41]=[C:42]([C:44]([F:46])([F:47])[F:45])[CH:43]=1)[C:6]([N:8]1[CH2:12][C@@:11]([CH2:20][CH2:21][N:22]2[CH2:27][CH2:26][C:25]3([C:35]4[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=4)[CH2:29][C@@H:28]3[O:36][CH2:37][C:38]([N:65]([CH2:66][CH2:67][CH2:68][CH2:69][OH:70])[CH3:64])=[O:39])[CH2:24][CH2:23]2)([C:13]2[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=2)[O:10][CH2:9]1)=[O:7]

Komponenten

8

Edukt 5

HCID 8471TriethylamineHCID 62493Pivaloyl chlorideHCID 516892Sodium BicarbonateHCID 98339374-(Methylamino)butan-1-olHCID 86663420{[(2S)-1'-{2-[(5R)-3-[3,5-Bis(trifluoromethyl)benzoyl]-5-(4-fluorophenyl)-1,3-oxazolidin-5-yl]ethyl}-2,3-dihydrospiro[indene-1,4'-piperidin]-2-yl]oxy}acetic acid

Produkt 1

HCID 866634492-{[(2S)-1'-{2-[(5R)-3-[3,5-Bis(trifluoromethyl)benzoyl]-5-(4-fluorophenyl)-1,3-oxazolidin-5-yl]ethyl}-2,3-dihydrospiro[indene-1,4'-piperidin]-2-yl]oxy}-N-(4-hydroxybutyl)-N-methylacetamideAusbeute 77,3 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6344DichloromethaneLösungsmittel2×HCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

The compound (400 mg, 0.576 mmol) obtained in Example 1j was dissolved in dichloromethane (30 mL), triethylamine (0.12 mL, 1.04 mmol) and pivaloyl chloride (0.11 mL, 0.864 mmol) were added under ice cooling, and the mixture was stirred at the same temperature under a nitrogen atmosphere for 15 minutes. Subsequently, a solution of 4-(methylamino)butan-1-ol (178 mg, 1.73 mmol) in dichloromethane (2 mL) was added under ice cooling, and the mixture was stirred at room temperature under a nitrogen atmosphere for 16 hours. After the reaction was completed, a saturated aqueous sodium hydrogencarbonate solution was added, and ethyl acetate was further added to separate the layers. The resulting organic layer was separated, washed with saturated sodium chloride solution, and then dried with anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by NH silica gel column chromatography (hexane:ethyl acetate, 10:1, v/v) to give the title compound (347 mg; yield, 77%) as a colorless oily substance.

Aufarbeitung

  1. stirringthe mixture was stirred at room temperature under a nitrogen atmosphere for 16 hours
  2. customto separate the layers
  3. customThe resulting organic layer was separated
  4. washwashed with saturated sodium chloride solution
  5. dry with materialdried with anhydrous sodium sulfate
  6. customthe solvent was evaporated under reduced pressure
  7. customThe residue was purified by NH silica gel column chromatography (hexane:ethyl acetate, 10:1, v/v)

Quellen und Nachweise

ORD-Eintrag
ord-99cd551606824500ace81199c6033fb2
Quelldatensatz
uspto-grants-2013_07
Patentnummer
US08476253B2

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