Hydrochloric Acid → 4-[4-({(tert-butoxycarbonyl)[(1R)-1-(1-naphthyl)ethyl]amino}methyl)-3-phenylpiperidin-1-yl]-3,5-difluorobenzoic acid

HRID 1691765ノート

反応式

HRID 1691765 の反応式
[C:1]([O:5][C:6]([N:8]([CH2:21][CH:22]1[CH2:27][CH2:26][N:25]([C:28]2[C:37]([F:38])=[CH:36][C:31]([C:32]([O:34]C)=[O:33])=[CH:30][C:29]=2[F:39])[CH2:24][CH:23]1[C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1)[C@@H:9]([C:11]1[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[CH:14]=[CH:13][CH:12]=1)[CH3:10])=[O:7])([CH3:4])([CH3:3])[CH3:2].C1COCC1.[OH-].[Na+].Cl>CO>[C:1]([O:5][C:6]([N:8]([CH2:21][CH:22]1[CH2:27][CH2:26][N:25]([C:28]2[C:29]([F:39])=[CH:30][C:31]([C:32]([OH:34])=[O:33])=[CH:36][C:37]=2[F:38])[CH2:24][CH:23]1[C:40]1[CH:41]=[CH:42][CH:43]=[CH:44][CH:45]=1)[C@@H:9]([C:11]1[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[CH:14]=[CH:13][CH:12]=1)[CH3:10])=[O:7])([CH3:2])([CH3:3])[CH3:4]

参加物

6

反応物 4

HCID 313Hydrochloric AcidHCID 8028TetrahydrofuranHCID 14798Sodium HydroxideHCID 66906144methyl 4-[4-({(tert-butoxycarbonyl)[(1R)-1-(1-naphthyl)ethyl]amino}methyl)-3-phenylpiperidin-1-yl]-3,5-difluorobenzoate

生成物 1

HCID 669060884-[4-({(tert-butoxycarbonyl)[(1R)-1-(1-naphthyl)ethyl]amino}methyl)-3-phenylpiperidin-1-yl]-3,5-difluorobenzoic acid収率 96.5%

試薬・触媒・溶媒 1

HCID 887Methanol溶媒

実験手順

To a mixture of 247 mg of the crude methyl 4-[4-({(tert-butoxycarbonyl)[(1R)-1-(1-naphthyl)ethyl]amino}methyl)-3-phenylpiperidin-1-yl]-3,5-difluorobenzoate, 4.0 mL of THF, and 2.0 mL of methanol was added dropwise a 1 M aqueous sodium hydroxide solution at room temperature, followed by stirring overnight. The reaction mixture was neutralized by addition of 1 M hydrochloric acid, and then extracted with ethyl acetate, and the organic layer was dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (methanol-chloroform) to obtain 233 mg of 4-[4-({(tert-butoxycarbonyl)[(1R)-1-(1-naphthyl)ethyl]amino}methyl)-3-phenylpiperidin-1-yl]-3,5-difluorobenzoic acid as a white solid. FAB+: 601

後処理

  1. extractionextracted with ethyl acetate
  2. dry with materialthe organic layer was dried over anhydrous sodium sulfate
  3. filtrationAfter filtration
  4. concentrationthe filtrate was concentrated under reduced pressure
  5. customthe residue was purified by silica gel column chromatography (methanol-chloroform)

出典と根拠

ORDレコード
ord-22f9440104314ccc9d330697135a9d6c
出典データセット
uspto-grants-2012_04
特許番号
US08153658B2

反応ノート

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