Dichloromethane → (R)-{2-[1-(4-Bromo-2,6-dimethylphenyl)-3,5-diethyl-1H-pyrazol-4-yl methyl]-1,2,3,4-tetrahydro-isoquinolin-3-yl}-methanol

HRID 1740103Notes

Reaction equation

HRID 1740103 reaction equation
[Br:1][C:2]1[CH:7]=[C:6]([CH3:8])[C:5]([N:9]2[C:13]([CH2:14][CH3:15])=[C:12]([CH2:16]O)[C:11]([CH2:18][CH3:19])=[N:10]2)=[C:4]([CH3:20])[CH:3]=1.C(N(CC)CC)C.C(Cl)Cl.[OH:31][CH2:32][CH:33]1[CH2:42][C:41]2[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=2)[CH2:35][NH:34]1>CN(C)C=O>[Br:1][C:2]1[CH:7]=[C:6]([CH3:8])[C:5]([N:9]2[C:13]([CH2:14][CH3:15])=[C:12]([CH2:16][N:34]3[C@@H:33]([CH2:32][OH:31])[CH2:42][C:41]4[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=4)[CH2:35]3)[C:11]([CH2:18][CH3:19])=[N:10]2)=[C:4]([CH3:20])[CH:3]=1

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 8471TriethylamineHCID 3752277(1,2,3,4-Tetrahydro-isoquinolin-3-yl)-methanolHCID 218373201-(4-bromo-2,6-dimethylphenyl)-3,5-diethyl-1H-pyrazol-4-yl-methanol

Product 1

HCID 54272289(R)-{2-[1-(4-Bromo-2,6-dimethylphenyl)-3,5-diethyl-1H-pyrazol-4-yl methyl]-1,2,3,4-tetrahydro-isoquinolin-3-yl}-methanolYield 135.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

To an ice bath-chilled solution of [1-(4-bromo-2,6-dimethylphenyl)-3,5-diethyl-1H-pyrazol-4-yl-methanol (770 mg, 2.3 mmol) and triethylamine (0.382 ml, 2.7 mmol) in methylene chloride (10 ml) methane sulfonyl chloride (0.1 94 ml, 2.5 mmol) was added dropwise. After stirring the reaction at 0-5° C. for 30 minutes, (+)-3-hydroxymethyl-1,2,3,4-tetrahydroisoquinoline (1.49 g, 9.1 mmol) and anhydrous N,N-dimethylformamide (2.2 ml) were added, and the resulting reaction mixture was heated (50° C. oil bath) for 21 hours. The solvent was removed in vacuo, and the residue was extracted with ethyl acetate/water (10 ml of each). The aqueous phase was then extracted twice with equal-volume portions of fresh ethyl acetate. The combined organic layers were dried over anhydrous sodium sulfate and concentrated in vacuo to afford a yellow oil (1.5 g). Flash chromatography (silica gel, 40 micron mesh; elution with ethyl acetate/hexane=1:5 in volume) afforded the title compound (0.45 g) as a light yellow oil.

Workup

  1. customthe reaction at 0-5° C. for 30 minutes
  2. customthe resulting reaction mixture
  3. customThe solvent was removed in vacuo
  4. extractionthe residue was extracted with ethyl acetate/water (10 ml of each)
  5. extractionThe aqueous phase was then extracted twice with equal-volume portions of fresh ethyl acetate
  6. dry with materialThe combined organic layers were dried over anhydrous sodium sulfate
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-3bdcaf4d63104304b3be77c91c479f14
Source dataset
uspto-grants-1999_10
Patent number
US05968944

Reaction notes

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