Chloromethyl chloroformate → (2R,3R)-3-[4-(4-cyanophenyl)thiazol-2-yl]-2-(2,4-difluorophenyl)-1-(1H-1,2,4-triazol-1-yl)-2-[[chloromethoxy]carbonyloxy]butane

HRID 1386816노트

반응식

HRID 1386816 반응식
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([C:9]2[N:10]=[C:11]([C@H:14]([CH3:31])[C@:15]([C:23]3[CH:28]=[CH:27][C:26]([F:29])=[CH:25][C:24]=3[F:30])([OH:22])[CH2:16][N:17]3[CH:21]=[N:20][CH:19]=[N:18]3)[S:12][CH:13]=2)=[CH:5][CH:4]=1)#[N:2].[H-].[K+].Cl[C:35]([O:37][CH2:38][Cl:39])=[O:36]>C1COCC1.CCOC(C)=O>[C:1]([C:3]1[CH:8]=[CH:7][C:6]([C:9]2[N:10]=[C:11]([C@H:14]([CH3:31])[C@:15]([C:23]3[CH:28]=[CH:27][C:26]([F:29])=[CH:25][C:24]=3[F:30])([O:22][C:35]([O:37][CH2:38][Cl:39])=[O:36])[CH2:16][N:17]3[CH:21]=[N:20][CH:19]=[N:18]3)[S:12][CH:13]=2)=[CH:5][CH:4]=1)#[N:2]

참가 물질

6

반응물 3

HCID 62754Chloromethyl chloroformateHCID 82127Potassium hydrideHCID 467825Ravuconazole

생성물 1

HCID 12046103(2R,3R)-3-[4-(4-cyanophenyl)thiazol-2-yl]-2-(2,4-difluorophenyl)-1-(1H-1,2,4-triazol-1-yl)-2-[[chloromethoxy]carbonyloxy]butane수율 111.6%

시약·촉매·용매 2

HCID 8028Tetrahydrofuran용매HCID 8857Ethyl Acetate용매

실험 절차

(2R,3R)-3-[4-(4-cyanophenyl)thiazol-2-yl]-2-(2,4-difluorophenyl)-1-(1H-1,2,4-triazol-1-yl)butan-2-ol (5.8 mmol) was added to a suspension of potassium hydride (7 mmol) in THF at 0° C. and was allowed to stir for 0.5 hours. Choromethyl chloroformate (5.8 mmol, in 2mL THF) was added dropwise and the reaction was allowed to warm to room temperature and stirred for 4 hours. The crude reaction was diluted with EtOAc, and was sequentially washed with H2O, 0.1N HCl, H2O, and brine. The organic layer was dried over MgSO4 and was concentrated to afford 3.43 g of the subtitled product as a pale yellow solid. 1H NMR (DMSO) δ8.47 (s, 1H), 8.29 (s, 1H), 8.08 (s, 1H), 7.97 (d, 2H, J=8), 7.88 (d, 2H, J=8), 7.26-7.12 (m, 3H), 5.93 (d, 1H, J=6), 5.90 (d, 1H, J=6), 5.70 (d, J=1H, J=15), 5.36 (d, 1H, J=15), 4.02 (q, 1H, J=7), and 1.48 (d, 3H, J=7); MS (MH+=530).

후처리

  1. stirringstirred for 4 hours
  2. customThe crude reaction
  3. washwas sequentially washed with H2O, 0.1N HCl, H2O, and brine
  4. dry with materialThe organic layer was dried over MgSO4
  5. concentrationwas concentrated

출처 및 근거

ORD 기록
ord-0b8b668c883b4b75958e674dd315852d
출처 데이터셋
uspto-grants-2001_07
특허 번호
US06265584B1

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