Sodium Bicarbonate → ethyl 4-[(2-chloro-4,4-difluoro-spiro[5H-thieno[2,3-c]pyran-7,4'-piperidine]-1'-yl)methyl]-1-(3-fluoro-2-pyridyl)pyrazole-3-carboxylate

HRID 1517615노트

반응식

HRID 1517615 반응식
[F:1][C:2]1[C:3]([N:8]2[CH:12]=[C:11]([CH:13]=O)[C:10]([C:15]([O:17][CH2:18][CH3:19])=[O:16])=[N:9]2)=[N:4][CH:5]=[CH:6][CH:7]=1.[Cl:20][C:21]1[S:25][C:24]2[C:26]3([O:32][CH2:33][C:34]([F:36])([F:35])[C:23]=2[CH:22]=1)[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]3.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)(O)[O-].[Na+]>ClCCCl>[Cl:20][C:21]1[S:25][C:24]2[C:26]3([O:32][CH2:33][C:34]([F:35])([F:36])[C:23]=2[CH:22]=1)[CH2:27][CH2:28][N:29]([CH2:13][C:11]1[C:10]([C:15]([O:17][CH2:18][CH3:19])=[O:16])=[N:9][N:8]([C:3]2[C:2]([F:1])=[CH:7][CH:6]=[CH:5][N:4]=2)[CH:12]=1)[CH2:30][CH2:31]3

참가 물질

6

반응물 4

HCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 582685982'-Chloro-4',4'-difluoro-4',5'-dihydrospiro[piperidine-4,7'-[7H]thieno[2,3-c]pyran]HCID 58268637Ethyl 1-(3-fluoro-2-pyridyl)-4-formyl-pyrazole-3-carboxylate

생성물 1

HCID 58268607ethyl 4-[(2-chloro-4,4-difluoro-spiro[5H-thieno[2,3-c]pyran-7,4'-piperidine]-1'-yl)methyl]-1-(3-fluoro-2-pyridyl)pyrazole-3-carboxylate수율 85.4%

시약·촉매·용매 1

HCID 111,2-Dichloroethane용매

실험 절차

To a solution of ethyl 1-(3-fluoro-2-pyridyl)-4-formyl-pyrazole-3-carboxylate (342.5 mg) in 1,2-dichloroethane (6.7 mL), 2-chloro-4,4-difluoro-spiro[5H-thieno[2,3-c]pyran-7,4′-piperidine] (280 mg, 1 mmol) is added. The mixture is stirred for 10 min. Then, sodium triacetoxyborohydride (442 mg) is added and the mixture is stirred overnight at room temperature. Sodium bicarbonate (saturated aqueous solution) is added and the organic phase extracted with dichloromethane, dried over magnesium sulfate and solvent evaporated in vacuo. Crude is purified by normal phase Isco chromatography using as eluent ethyl acetate and hexane to give 450 mg of ethyl 4-[(2-chloro-4,4-difluoro-spiro[5H-thieno[2,3-c]pyran-7,4′-piperidine]-1′-yl)methyl]-1-(3-fluoro-2-pyridyl)pyrazole-3-carboxylate. MS (m/z): 527 (M+1).

후처리

  1. stirringthe mixture is stirred overnight at room temperature
  2. extractionthe organic phase extracted with dichloromethane
  3. dry with materialdried over magnesium sulfate and solvent
  4. customevaporated in vacuo
  5. customCrude is purified by normal phase Isco chromatography

출처 및 근거

ORD 기록
ord-feb6416dc6a54922b698145fafb0f232
출처 데이터셋
uspto-grants-2012_07
특허 번호
US08232289B2

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