Triethylamine → Methyl 1-{[(4,4'-dichlorobiphenyl-3-yl)acetyl]amino}-4,4-difluorocyclohexanecarboxylate

HRID 1466450노트

반응식

HRID 1466450 반응식
Cl.[NH2:2][C:3]1([C:11]([O:13][CH3:14])=[O:12])[CH2:8][CH2:7][C:6]([F:10])([F:9])[CH2:5][CH2:4]1.C(N(CC)CC)C.[Cl:22][C:23]1[CH:28]=[CH:27][C:26]([C:29]2[CH:34]=[CH:33][C:32]([Cl:35])=[CH:31][CH:30]=2)=[CH:25][C:24]=1[CH2:36][C:37](O)=[O:38].P(Cl)(Cl)(Cl)=O>O1CCCC1>[Cl:22][C:23]1[CH:28]=[CH:27][C:26]([C:29]2[CH:30]=[CH:31][C:32]([Cl:35])=[CH:33][CH:34]=2)=[CH:25][C:24]=1[CH2:36][C:37]([NH:2][C:3]1([C:11]([O:13][CH3:14])=[O:12])[CH2:8][CH2:7][C:6]([F:10])([F:9])[CH2:5][CH2:4]1)=[O:38]

참가 물질

6

반응물 4

HCID 8471Triethylamine2회HCID 24813Phosphorus oxychlorideHCID 60196672Methyl 1-amino-4,4-difluorocyclohexanecarboxylate hydrochlorideHCID 67372946(4,4'-Dichlorobiphenyl-3-yl)acetic acid

생성물 1

HCID 86707850Methyl 1-{[(4,4'-dichlorobiphenyl-3-yl)acetyl]amino}-4,4-difluorocyclohexanecarboxylate

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

2.53 g (11 mmol) of the compound from Example 4A were initially charged in 50 ml of absolute tetrahydrofuran (THF). 3.07 ml of triethylamine were added dropwise at 20° C., the mixture was stirred for 5 min, and 2.81 g (10 mmol) of (4,4′-dichlorobiphenyl-3-yl)acetic acid (EP 1943218 A1 and US 2009/215624 A1) were added. After 15 min, a further 2.3 ml of triethylamine were added, followed immediately by the dropwise addition of 0.58 ml (6.2 mmol) of phosphorus oxychloride, and the mixture was stirred under reflux for 30 min. The mixture was concentrated under reduced pressure and the residue was purified by means of flash chromatography on silica gel using the mobile phase n-hexane/ethyl acetate 1:1. This gave 3.3 g (59% of theory) of the title compound of melting point 146-147° C.

후처리

  1. waitAfter 15 min
  2. stirringthe mixture was stirred
  3. temperatureunder reflux for 30 min
  4. concentrationThe mixture was concentrated under reduced pressure
  5. customthe residue was purified by means of flash chromatography on silica gel using the mobile phase n-hexane/ethyl acetate 1:1

출처 및 근거

ORD 기록
ord-187b1c4383c34993b8ae21a9b59c1cbf
출처 데이터셋
uspto-grants-2015_04
특허 번호
US09000026B2

반응 노트

불러오는 중…