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

HRID 251612노트

반응식

HRID 251612 반응식
[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]

참가 물질

7

반응물 4

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

생성물 1

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

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매

반응 조건

온도
80 °C

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-f21680502d224645a341c5f616292595
출처 데이터셋
uspto-grants-2011_01
특허 번호
US07863454B2

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