Dimethylformamide → (R*)-1-[1-((9RS, 10RS)-2-Chloro-9,10-dihydro-9,10-methanoanthracen-9-ylcarbonyl)-4-piperidyl]-1-(3-pyridyl)ethanol

HRID 862734ノート

反応式

HRID 862734 の反応式
[Cl:1][C:2]1[CH:15]=[CH:14][C:13]2[C@H:12]3[CH2:16][C@:5]([C:17](O)=[O:18])([C:6]4[C:11]3=[CH:10][CH:9]=[CH:8][CH:7]=4)[C:4]=2[CH:3]=1.C(Cl)(=O)C(Cl)=O.CN(C)C=O.[NH:31]1[CH2:36][CH2:35][CH:34]([C@:37]([C:40]2[CH:41]=[N:42][CH:43]=[CH:44][CH:45]=2)([OH:39])[CH3:38])[CH2:33][CH2:32]1.C(N(CC)CC)C.[OH-].[Na+]>ClCCl.O1CCCC1>[Cl:1][C:2]1[CH:15]=[CH:14][C:13]2[CH:12]3[CH2:16][C:5]([C:17]([N:31]4[CH2:36][CH2:35][CH:34]([C@:37]([C:40]5[CH:41]=[N:42][CH:43]=[CH:44][CH:45]=5)([OH:39])[CH3:38])[CH2:33][CH2:32]4)=[O:18])([C:6]4[C:11]3=[CH:10][CH:9]=[CH:8][CH:7]=4)[C:4]=2[CH:3]=1

参加物

9

反応物 6

HCID 6228DimethylformamideHCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 65578Oxalyl chlorideHCID 53961295(R*)-1-(4-piperidyl)-1-(3-pyridyl)ethanolHCID 67637562(9S,10S)-2-chloro-9,10-dihydro-9,10-methano-9-anthracenecarboxylic acid

生成物 1

HCID 131720503(R*)-1-[1-((9RS, 10RS)-2-Chloro-9,10-dihydro-9,10-methanoanthracen-9-ylcarbonyl)-4-piperidyl]-1-(3-pyridyl)ethanol

試薬・触媒・溶媒 2

HCID 6344Dichloromethane溶媒2 回HCID 8028Tetrahydrofuran溶媒

実験手順

A solution of (9S,10S)-2-chloro-9,10-dihydro-9,10-methano-9-anthracenecarboxylic acid, prepared as in Example 11 (1.25 g, 4.61 mmol) in dichloromethane (20 mL) was treated with oxalyl chloride (731 mg, 5.76 mmol) and N,N-dimethylformamide (10 mg, 0.14 mmol). The resulting solution was warmed to reflux temperature for 2 h, then was cooled to room temperature and the excess reagent was evaporated in vacuo. The residue was dissolved in tetrahydrofuran (10 mL) and added dropwise to a solution of (R*)-1-(4-piperidyl)-1-(3-pyridyl)ethanol (950 mg, 4.61 mmol) and triethylamine (582 mg, 5.76 mmol) in tetrahydrofuran (15 mL) and dichloromethane (25 mL). The resulting mixture was stirred for 3 h at room temperature, then was poured into 1N aqueous sodium hydroxide (25 mL) and extracted with chloroform (3×100 mL) The organic extracts were washed sequentially with 1N aqueous sodium hydroxide (50 mL) and brine (50 mL), combined, dried over sodium sulfate, filtered and evaporated to leave a dark tan foam. Purification by flash chromatography (eluant: 1:1 hexane/acetone) afforded the title amide as an off white foam (2.00 g, 4.36 mmol, 95%). CIMS: m/z 461 ((M+H)+, 37Cl, 33%), 460 ((M+H+1)+, 35Cl, 28), 459 ((M+M)+, 35Cl, 100).

後処理

  1. temperatureThe resulting solution was warmed
  2. temperatureto reflux temperature for 2 h
  3. customthe excess reagent was evaporated in vacuo
  4. dissolutionThe residue was dissolved in tetrahydrofuran (10 mL)
  5. extractionextracted with chloroform (3×100 mL) The organic extracts
  6. washwere washed sequentially with 1N aqueous sodium hydroxide (50 mL) and brine (50 mL)
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. customevaporated
  10. customto leave a dark tan foam
  11. customPurification by flash chromatography (eluant: 1:1 hexane/acetone)

出典と根拠

ORDレコード
ord-5c41dbb99017425b8a124edae98fc7fc
出典データセット
uspto-grants-1998_02
特許番号
US05719166

反応ノート

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