Triethylamine → {[3-(4',5'-Difluoro-2'-methoxy-biphenyl-4-yloxymethyl)-4-fluoro-benzoyl]-methyl-amino}-acetic acid ethyl ester

HRID 1665260노트

반응식

HRID 1665260 반응식
[F:1][C:2]1[C:7]([F:8])=[CH:6][C:5]([C:9]2[CH:14]=[CH:13][C:12]([O:15][CH2:16][C:17]3[CH:18]=[C:19]([CH:23]=[CH:24][C:25]=3[F:26])[C:20](O)=[O:21])=[CH:11][CH:10]=2)=[C:4]([O:27][CH3:28])[CH:3]=1.Cl.[CH2:30]([O:32][C:33](=[O:37])[CH2:34][NH:35][CH3:36])[CH3:31].C1C=NC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.C(N(CC)CC)C>C(Cl)Cl>[CH2:30]([O:32][C:33](=[O:37])[CH2:34][N:35]([C:20](=[O:21])[C:19]1[CH:23]=[CH:24][C:25]([F:26])=[C:17]([CH2:16][O:15][C:12]2[CH:11]=[CH:10][C:9]([C:5]3[CH:6]=[C:7]([F:8])[C:2]([F:1])=[CH:3][C:4]=3[O:27][CH3:28])=[CH:14][CH:13]=2)[CH:18]=1)[CH3:36])[CH3:31]

참가 물질

7

반응물 5

HCID 8471TriethylamineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 171173Ethyl N-methylaminoacetate hydrochlorideHCID 181649HOAtHCID 582711923-(4',5'-Difluoro-2'-methoxybiphenyl-4-yloxymethyl)-4-fluorobenzoic acid

생성물 1

HCID 67152333{[3-(4',5'-Difluoro-2'-methoxy-biphenyl-4-yloxymethyl)-4-fluoro-benzoyl]-methyl-amino}-acetic acid ethyl ester수율 77.3%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

To a mixture of 3-(4′,5′-difluoro-2′-methoxybiphenyl-4-yloxymethyl)-4-fluorobenzoic acid (0.3 g, 0.77 mmol) and N-methyl-glycine ethyl ester hydrochloride (0.7 g, 4.5 mmol) in methylene chloride (40 mL) was added HOAT (0.2 g, 1.46 mmol), EDCI (0.3 g, 1.56 mmol) and triethylamine (1.4 mL, 10 mmol). The mixture was stirred at room temperature for 3 hrs and extracted with methylene chloride and dilute hydrochloric acid. The organic layer was dried and concentrated. The residue was purified through flash column chromatography (80 g silica gel, 5% to 60% ethyl acetate in hexanes over 25 minutes) to give amorphous material as {[3-(4′,5′-difluoro-2′-methoxy-biphenyl-4-yloxymethyl)-4-fluoro-benzoyl]-methyl-amino}-acetic acid ethyl ester (0.29 g, 77%).

후처리

  1. extractionextracted with methylene chloride and dilute hydrochloric acid
  2. customThe organic layer was dried
  3. concentrationconcentrated
  4. customThe residue was purified through flash column chromatography (80 g silica gel, 5% to 60% ethyl acetate in hexanes over 25 minutes)

출처 및 근거

ORD 기록
ord-2b414125536f4b669eaced69d24f945b
출처 데이터셋
uspto-grants-2011_10
특허 번호
US08039495B2

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