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

HRID 862734Notes

Reaction equation

HRID 862734 reaction equation
[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

Participants

9

Reactant 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

Product 1

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

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

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).

Workup

  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)

Sources & evidence

ORD record
ord-5c41dbb99017425b8a124edae98fc7fc
Source dataset
uspto-grants-1998_02
Patent number
US05719166

Reaction notes

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