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 1517615ノート

反応式

HRID 1517615 の反応式
[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

参加物

6

反応物 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

生成物 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-carboxylate収率 85.4%

試薬・触媒・溶媒 1

HCID 111,2-Dichloroethane溶媒

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-feb6416dc6a54922b698145fafb0f232
出典データセット
uspto-grants-2012_07
特許番号
US08232289B2

反応ノート

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