Oxalyl chloride → HCID 9902489, compound

HRID 1826678Notes

Reaction equation

HRID 1826678 reaction equation
[CH:1]1([C:7]2[CH:15]=[CH:14][C:10]([C:11]([OH:13])=O)=[CH:9][CH:8]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C(Cl)(=O)C(Cl)=O.[S:22]1[C:31]2[CH2:30][CH2:29][CH2:28][CH2:27][NH:26][C:25]=2[CH:24]=[CH:23]1.CCN(C(C)C)C(C)C.C1(C2C=CC(C(Cl)=O)=CC=2)CCCCC1>O1CCCC1.ClCCl.CN(C)C=O>[CH:1]1([C:7]2[CH:8]=[CH:9][C:10]([C:11]([N:26]3[CH2:27][CH2:28][CH2:29][CH2:30][C:31]4[S:22][CH:23]=[CH:24][C:25]3=4)=[O:13])=[CH:14][CH:15]=2)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1

Participants

9

Reactant 5

HCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 883374-Cyclohexylbenzoic acidHCID 118049715,6,7,8-Tetrahydro-4H-thieno[3,2-B]azepineHCID 218908474-Cyclohexylbenzoyl chloride

Product 1

HCID 9902489HCID 9902489, compoundYield 81.3%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of 4-cyclohexyl-benzoic acid (0.479g) in tetrahydrofuran (10 ml) was treated with N,N-dimethylformamide (20 μl) followed by dropwise addition of oxalyl chloride (0.260 ml). When the gas evolution stopped the solution was warmed to reflux for 5 minutes, then cooled and concentrated in vacuo to an oil. The oil was diluted with tetrahydrofuran (5 ml) and again concentrated in vacuo. This cycle was repeated one more time and then the oil was dissolved in dichloromethane (15 ml). A solution of 5,6,7,8-tetrahydro-4H-thieno[3,2-b]azepine (0.300 g) and Hunig's base (1.1 equiv.) in dichloromethane (25 ml) was cooled to 0° and treated dropwise with the previously prepared solution of 4-cyclohexylbenzoyl chloride. The reaction was stirred overnight as the temperature was allowed to return to room temperature. The solution was washed sequentially with 0.1N hydrochloric acid, 50% saturated aqueous sodium bicarbonate solution and brine. The organic layer was dried over anhydrous sodium sulfate, filtered and evaporated in vacuo. The residual oil was flash chromatographed on silica gel using 15% ethyl acetate in hexanes as the eluant to provide the title compound (0.54 g) as an orange tinged solid.

Workup

  1. temperaturewas warmed
  2. temperatureto reflux for 5 minutes
  3. temperaturecooled
  4. concentrationconcentrated in vacuo to an oil
  5. additionThe oil was diluted with tetrahydrofuran (5 ml)
  6. concentrationagain concentrated in vacuo
  7. dissolutionthe oil was dissolved in dichloromethane (15 ml)
  8. customto return to room temperature
  9. washThe solution was washed sequentially with 0.1N hydrochloric acid, 50% saturated aqueous sodium bicarbonate solution and brine
  10. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  11. filtrationfiltered
  12. customevaporated in vacuo
  13. customchromatographed on silica gel using 15% ethyl acetate in hexanes as the eluant

Sources & evidence

ORD record
ord-62add9b2d69d436ca26fed8ee9a5fa78
Source dataset
uspto-grants-2006_05
Patent number
US07053083B2

Reaction notes

Loading…