Water → 1-(Biphenyl-4-ylcarbamoyl)-cyclopropanecarboxylic acid

HRID 1093709

반응식

HRID 1093709 반응식
O[Li].O.C[O:5][C:6]([C:8]1([C:11](=[O:25])[NH:12][C:13]2[CH:18]=[CH:17][C:16]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)=[CH:15][CH:14]=2)[CH2:10][CH2:9]1)=[O:7].C1COCC1.O>CO>[C:16]1([C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=2)[CH:17]=[CH:18][C:13]([NH:12][C:11]([C:8]2([C:6]([OH:7])=[O:5])[CH2:10][CH2:9]2)=[O:25])=[CH:14][CH:15]=1

참가 물질

6

반응물 4

HCID 962WaterHCID 8028TetrahydrofuranHCID 168937Lithium hydroxide, monohydrateHCID 578758101-(Biphenyl-4-ylcarbamoyl)-cyclopropanecarboxylic acid methyl ester

생성물 1

HCID 578743681-(Biphenyl-4-ylcarbamoyl)-cyclopropanecarboxylic acid수율 33%

시약·촉매·용매 1

HCID 887Methanol용매

실험 절차

KOH (420 mg, 7.5 mmol) was added to a solution cyclopropane-1,1-dicarboxylic acid diethyl ester (1 g, 6.3 mmol) in methanol (7 mL). The reaction mixture was stirred for 4 hours at ambient temperature then concentrated. The resulting residue was diluted with water, acidified with conc. HCl and the product was extracted with dichloromethane. The dichloromethane layer was dried over sodium sulfate and concentrated under reduced pressure to afford 680 mg (75%) of cyclopropane-1,1-dicarboxylic acid methyl ester. HOBt (764 mg, 5.6 mmol), DMAP (1.72 g, 14.15 mmol) and EDCI.HCl (1.08 g, 5.6 mmol) followed by biphenyl-4-ylamine (957 mg, 5.6 mmol) were added to a stirred solution of cyclopropane-1,1-dicarboxylic acid methyl ester (680 mg, 4.7 mmol) in DMF (7 mL) and the resulting mixture was stirred at ambient temperature overnight. The mixture was then diluted with water and the product was extracted with ethyl acetate. The ethylacetate layer was washed with brine solution and concentrated to afford 1.1 g (79%) of 1-(biphenyl-4-ylcarbamoyl)-cyclopropanecarboxylic acid methyl ester. LiOH.H2O (234 mg, 5.5 mmol) was added to a solution of 1-(biphenyl-4-ylcarbamoyl)-cyclopropanecarboxylic acid methyl ester (1.1 g, 3.7 mmol) in a mixture of methanol (5 mL), THF (11 mL) and H2O (3 mL) and the resulting mixture was stirred for 2 hours at ambient temperature. The reaction mixture was then concentrated and the residue was diluted with water, acidified with conc. HCl. The resulting precipitate was isolated by filtration and dried to afford 340 mg (33%) of 1-(biphenyl-4-ylcarbamoyl)-cyclopropane carboxylic acid.

후처리

  1. concentrationThe reaction mixture was then concentrated
  2. additionthe residue was diluted with water
  3. customThe resulting precipitate was isolated by filtration
  4. customdried

출처 및 근거

ORD 기록
ord-b90557bbb96743089df95e33fba42774
출처 데이터셋
uspto-grants-2012_03
특허 번호
US08129376B2

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