Methanesulfonyl chloride → 3-[4-(3,6-Dihydro-4-phenyl-1(2H)-pyridinyl)-1-butynyl]quinoline

HRID 327413Notes

Reaction equation

HRID 327413 reaction equation
[N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[C:3]([C:11]#[C:12][CH2:13][CH2:14]O)[CH:2]=1.C(N(CC)C(C)C)(C)C.CS(Cl)(=O)=O.[C:30]1([C:36]2[CH2:37][CH2:38][NH:39][CH2:40][CH:41]=2)[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1.C(=O)(O)[O-].[Na+]>CN(C)C1C=CN=CC=1>[C:30]1([C:36]2[CH2:41][CH2:40][N:39]([CH2:14][CH2:13][C:12]#[C:11][C:3]3[CH:2]=[N:1][C:10]4[C:5]([CH:4]=3)=[CH:6][CH:7]=[CH:8][CH:9]=4)[CH2:38][CH:37]=2)[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1

Participants

7

Reactant 5

HCID 31297Methanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 825531,2,3,6-Tetrahydro-4-phenylpyridineHCID 516892Sodium BicarbonateHCID 106317924-(3-Quinolinyl)-3-butyn-1-ol

Product 1

HCID 99058843-[4-(3,6-Dihydro-4-phenyl-1(2H)-pyridinyl)-1-butynyl]quinoline

Reagents, catalysts & solvents 1

HCID 142844-(Dimethylamino)pyridineCatalyst

Conditions

Temperature
0 °C

Procedure

A solution of the alcohol prepared in Step (a) (1.98 g, 0.01 mol), N,N-diisopropylethylamine (3.5 mL, 0.02 mol) and a catalytic amount of 4-dimethylaminopyridine is cooled to 0° C., and methanesulfonyl chloride (0.8 mL, 0.0105 mol) is added dropwise. The solution is stirred at 0° C. for 18 hours, and then concentrated under reduced pressure. The residue is taken up in dimethylformamide (20 mL), and to this solution is added 4-phenyl-1,2,3,6-tetrahydropyridine (2.41 g, 0.015 mol) and sodium bicarbonate (3.4 g, 0.04 mol). The mixture is heated at 40° C. for 5 hours, and the solvent is removed under reduced pressure. The residue is partitioned between 50 mL of ethyl acetate and 50 mL of water. The aqueous layer is extracted with 50 mL of ethyl acetate and the combined organic layers are dried (sodium sulfate), and the solvent is removed in vacuo. The residue is chromatographed (silica gel, 2% methanol/98% dichloromethane) to give the title compound, containing 0.4 mol of water; mp 94.3°-95.8° C.

Workup

  1. concentrationconcentrated under reduced pressure
  2. temperatureThe mixture is heated at 40° C. for 5 hours
  3. customthe solvent is removed under reduced pressure
  4. customThe residue is partitioned between 50 mL of ethyl acetate and 50 mL of water
  5. extractionThe aqueous layer is extracted with 50 mL of ethyl acetate
  6. dry with materialthe combined organic layers are dried (sodium sulfate)
  7. customthe solvent is removed in vacuo
  8. customThe residue is chromatographed (silica gel, 2% methanol/98% dichloromethane)

Sources & evidence

ORD record
ord-12fa124988f441f5b14a33aee6c819ba
Source dataset
uspto-grants-1993_12
Patent number
US05273977

Reaction notes

Loading…