Water → 4-Azetidin-1-yl-6-(2,6-diethyl-phenyl)-2-methyl-nicotinic acid methyl ester

HRID 1392643ノート

反応式

HRID 1392643 の反応式
[CH2:1]([O:3][C:4](=[O:23])[C:5]1[C:10](Cl)=[CH:9][C:8]([C:12]2[C:17]([CH2:18][CH3:19])=[CH:16][CH:15]=[CH:14][C:13]=2[CH2:20][CH3:21])=[N:7][C:6]=1[CH3:22])C.Cl.[NH:25]1[CH2:28][CH2:27][CH2:26]1.C([O-])([O-])=O.[K+].[K+].O>CN(C=O)C.CCOC(C)=O>[CH3:1][O:3][C:4](=[O:23])[C:5]1[C:10]([N:25]2[CH2:28][CH2:27][CH2:26]2)=[CH:9][C:8]([C:12]2[C:17]([CH2:18][CH3:19])=[CH:16][CH:15]=[CH:14][C:13]=2[CH2:20][CH3:21])=[N:7][C:6]=1[CH3:22]

参加物

7

反応物 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 12308726Azetidine hydrochlorideHCID 59678345Ethyl 4-chloro-6-(2,6-diethylphenyl)-2-methylnicotinate

生成物 1

HCID 669935764-Azetidin-1-yl-6-(2,6-diethyl-phenyl)-2-methyl-nicotinic acid methyl ester

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
80 °C

実験手順

A mixture of 4-chloro-6-(2,6-diethyl-phenyl)-2-methyl-nicotinic acid methyl ester (Example 2, step 1) (500 mg, 1.57 mmol), azetidine hydrochloride (588 mg, 6.29 mmol) and K2CO3 (1.08 g, 7.87 mmol) in DMF (5 mL) is heated at 80° C. in a sealed tube overnight. On cooling, water (20 mL) and EtOAc (20 mL) are added. The organic layer is separated and the aqueous layer is extracted with EtOAc (10 mL). The combined organic layer is washed with water, dried, and concentrated to give 4-azetidin-1-yl-6-(2,6-diethyl-phenyl)-2-methyl-nicotinic acid methyl ester as a crude product. A solution of LiAlH4 (1M in THF, 4.5 mL) is added to a solution of this crude product in THF (5 mL). The reaction mixture is stirred at room temperature overnight, diluted with ether (10 mL), and the reaction quenched with solid Na2SO4.10H2O (1.0 g). The resulting mixture is stirred for 1 hour, filtered through celite and concentrated at reduced pressure. The crude product is purified by PTLC (10% MeOH in CH2Cl2) to give the title product. 1H NMR (CDCl3) 7.20 (t, 1H), 7.10 (d, 2H), 6.09 (s, 1H), 4.66 (s, 2H), 4.17 (t, 4H), 2.58 (s, 3H), 2.38 (m, 6H), 1.08 (t, 6H).

後処理

  1. temperatureOn cooling
  2. customThe organic layer is separated
  3. extractionthe aqueous layer is extracted with EtOAc (10 mL)
  4. washThe combined organic layer is washed with water
  5. customdried
  6. concentrationconcentrated

出典と根拠

ORDレコード
ord-412c677a80ad4724afd55e77011668cb
出典データセット
uspto-grants-2008_03
特許番号
US07342115B2

反応ノート

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