Triethylamine → 1-({(1S,3R)-1-Isopropyl-3-[(3-methoxytetrahydro-2H-pyran-4-yl)amino]cyclopentyl}carbonyl)-4-[2-(trifluoromethyl)phenyl]piperidin-4-ol

HRID 1044578ノート

反応式

HRID 1044578 の反応式
Cl.[NH2:2][C@@H:3]1[CH2:7][CH2:6][C@@:5]([C:11]([N:13]2[CH2:18][CH2:17][C:16]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=3[C:26]([F:29])([F:28])[F:27])([OH:19])[CH2:15][CH2:14]2)=[O:12])([CH:8]([CH3:10])[CH3:9])[CH2:4]1.[CH3:30][O:31][CH:32]1[C:37](=O)[CH2:36][CH2:35][O:34][CH2:33]1.C([N:41](CC)CC)C.[C:46](O[BH-](OC(=O)C)OC(=O)C)(=[O:48])C.[Na+].C([O-])(O)=O.[Na+]>C(Cl)Cl>[NH4+:2].[OH-:12].[NH4+:41].[OH-:31].[CH3:46][OH:48].[CH:8]([C@:5]1([C:11]([N:13]2[CH2:18][CH2:17][C:16]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=3[C:26]([F:29])([F:27])[F:28])([OH:19])[CH2:15][CH2:14]2)=[O:12])[CH2:6][CH2:7][C@@H:3]([NH:2][CH:37]2[CH2:36][CH2:35][O:34][CH2:33][CH:32]2[O:31][CH3:30])[CH2:4]1)([CH3:10])[CH3:9]

参加物

9

反応物 5

HCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 235336103-Methoxyoxan-4-oneHCID 689309271-{[(1S,3R)-3-amino-1-isopropylcyclopentyl]carbonyl}-4-[2-(trifluoromethyl)phenyl]piperidin-4-ol hydrochloride

生成物 3

HCID 14923Ammonium HydroxideHCID 116492051-({(1S,3R)-1-Isopropyl-3-[(3-methoxytetrahydro-2H-pyran-4-yl)amino]cyclopentyl}carbonyl)-4-[2-(trifluoromethyl)phenyl]piperidin-4-ol収率 58.5%HCID 21894508Ammonium hydroxide methanol収率 1%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

To a solution of 1-{[(1S,3R)-3-amino-1-isopropylcyclopentyl]carbonyl}-4-[2-(trifluoromethyl)phenyl]piperidin-4-ol hydrochloride (50 mg, 0.1 mmol), 3-methoxytetrahydro-4H-pyran-4-one (45 mg, 0.34 mmol), and triethylamine (0.048 mL, 0.34 mmol) in methylene chloride (2 mL) was added sodium triacetoxyborohydride (0.073 g, 0.34 mmol). After being stirred overnight at room temperature, a saturated solution of NaHCO3 was added. The solution was extracted with methylene chloride three times. The combined extracts were dried (MgSO4), filtered, and concentrated. Purification by flash chromatography on silica gel (0-20% B over 15 min. Bottle A=1% NH4OH/2% MeOH/EtOAc, Bottle B=1% NH4OH/MeOH) afforded 15 mg of the desired product as an oil. MS calculated for C27H39F3N2O4: (M+H) 513; found 513.2.

後処理

  1. extractionThe solution was extracted with methylene chloride three times
  2. dry with materialThe combined extracts were dried (MgSO4)
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customPurification by flash chromatography on silica gel (0-20% B over 15 min

出典と根拠

ORDレコード
ord-1def7e8311cb4c3e935e3626f9469794
出典データセット
uspto-grants-2013_10
特許番号
US08563582B2

反応ノート

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