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

HRID 1665260ノート

反応式

HRID 1665260 の反応式
[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]

参加物

7

反応物 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

生成物 1

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

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

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%).

後処理

  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)

出典と根拠

ORDレコード
ord-2b414125536f4b669eaced69d24f945b
出典データセット
uspto-grants-2011_10
特許番号
US08039495B2

反応ノート

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