1,2-Dichloroethane → (S)-3,5-dichloro-4-(2-(2-(6-chloronicotinoyloxy)acetoxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)ethyl)pyridine 1-oxide

HRID 1776650노트

반응식

HRID 1776650 반응식
[Cl:1][C:2]1[CH:3]=[N+:4]([O-:31])[CH:5]=[C:6]([Cl:30])[C:7]=1[CH2:8][C@@H:9]([C:15]1[CH:20]=[CH:19][C:18]([O:21][CH:22]([F:24])[F:23])=[C:17]([O:25][CH2:26][CH:27]2[CH2:29][CH2:28]2)[CH:16]=1)[O:10][C:11](=[O:14])[CH2:12][OH:13].[Cl:32][C:33]1[CH:41]=[CH:40][C:36]([C:37](O)=[O:38])=[CH:35][N:34]=1.C(Cl)CCl>C(Cl)Cl.CN(C1C=CN=CC=1)C>[Cl:30][C:6]1[CH:5]=[N+:4]([O-:31])[CH:3]=[C:2]([Cl:1])[C:7]=1[CH2:8][C@H:9]([O:10][C:11](=[O:14])[CH2:12][O:13][C:37](=[O:38])[C:36]1[CH:40]=[CH:41][C:33]([Cl:32])=[N:34][CH:35]=1)[C:15]1[CH:20]=[CH:19][C:18]([O:21][CH:22]([F:24])[F:23])=[C:17]([O:25][CH2:26][CH:27]2[CH2:29][CH2:28]2)[CH:16]=1

참가 물질

6

반응물 3

HCID 111,2-DichloroethaneHCID 792226-Chloronicotinic acidHCID 86679512(S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(2-hydroxyacetoxy)ethyl)pyridine 1-oxide

생성물 1

HCID 86679594(S)-3,5-dichloro-4-(2-(2-(6-chloronicotinoyloxy)acetoxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)ethyl)pyridine 1-oxide수율 78%

시약·촉매·용매 2

HCID 142844-(Dimethylamino)pyridine촉매HCID 6344Dichloromethane용매

실험 절차

To a mixture of (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(2-hydroxyacetoxy)ethyl)pyridine 1-oxide (See Scheme 21, step 6-9) (200 mg, 0.418 mmol), 6-chloronicotinic acid (72.5 mg, 0.460 mmol) and EDC (240 mg, 1.255 mmol) in dry DCM (10 ml), DMAP (51.1 mg, 0.418 mmol) was added, and stirring was continued for a week-end at room temperature. The solvent was evaporated; the residue was portioned between sat. sol. NaHCO3 and ethyl acetate, the organic phase was washed with brine, dried over sodium sulfate and evaporated, the residue was purified by flash chromatography on silica gel (eluent: DCM/MeOH/32% NH4OH 98/2/0.2) and (S)-3,5-dichloro-4-(2-(2-(6-chloronicotinoyloxy)acetoxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)ethyl)pyridine 1-oxide was obtained as a white solid (202 mg, 0.327 mmol, 78% yield, MS/ESI+ 617.2 [MH]+).

후처리

  1. additionwas added
  2. waitwas continued for a week
  3. customat room temperature
  4. customThe solvent was evaporated
  5. washthe organic phase was washed with brine
  6. dry with materialdried over sodium sulfate
  7. customevaporated
  8. customthe residue was purified by flash chromatography on silica gel (eluent: DCM/MeOH/32% NH4OH 98/2/0.2)

출처 및 근거

ORD 기록
ord-1e787623bf4447cc8b7c1621cd3a086f
출처 데이터셋
uspto-grants-2016_02
특허 번호
US09265768B2

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