Water → 2-(3-Chloropropyl)-4,4-dimethyl-1,2,3,4-tetrahydro 1isoquinolinone

HRID 864360Notes

Reaction equation

HRID 864360 reaction equation
C([Li])CCC.[CH3:6][C:7]1([CH3:18])[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[C:10](=[O:17])[NH:9][CH2:8]1.[Cl:19][CH2:20][CH2:21][CH2:22]Br.O>O1CCCC1>[Cl:19][CH2:20][CH2:21][CH2:22][N:9]1[CH2:8][C:7]([CH3:18])([CH3:6])[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[C:10]1=[O:17]

Participants

6

Reactant 4

HCID 962WaterHCID 80061-Bromo-3-chloropropaneHCID 218202994,4-Dimethyl-1,2,3,4-tetrahydroisoquinolin-1-oneHCID 178418339Butyllithium

Product 1

HCID 194189092-(3-Chloropropyl)-4,4-dimethyl-1,2,3,4-tetrahydro 1isoquinolinoneYield 45.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
25 °C

Procedure

2-(3-Chloropropyl)-4,4-dimethyl-1,2,3,4-tetrahydro-1-isoquinolinone may be obtained in the following manner: 25.7 cm3 of n-butyllithium (1.6 M in hexane) are added to a solution of 6 g of 4,4-dimethyl-1,2,3,4-tetrahydro-1-isoquinolinone in 120 cm3 of tetrahydrofuran, at -76° C. under a nitrogen stream. The reaction mixture is left for three hours at 0° C. 13 g of 1-chloro-3-bromopropane are then added and the mixture is stirred for 18 hours at a temperature of about 25° C. The reaction mixture is treated with 240 cm3 of water and extracted with three times 100 cm3 ethyl acetate. The combined organic phases are dried over magnesium sulphate and evaporated to dryness at 40° C. under reduced pressure (20 mm of mercury; 2.7 KPa). The residue is purified by flash chromatography on a silica column under a nitrogen stream at moderate pressure (0.5-1.5 bar) with a dichloromethane-methanol mixture (99.5-0.5 by volume) as eluent. 3.9 g of 2-(3-chloropropyl)-4,4-dimethyl-1,2,3,4-tetrahydro 1isoquinolinone are obtained; melting point =131° C.

Workup

  1. extractionextracted with three times 100 cm3 ethyl acetate
  2. dry with materialThe combined organic phases are dried over magnesium sulphate
  3. customevaporated to dryness at 40° C. under reduced pressure (20 mm of mercury; 2.7 KPa)
  4. customThe residue is purified by flash chromatography on a silica column under a nitrogen stream at moderate pressure (0.5-1.5 bar) with a dichloromethane-methanol mixture (99.5-0.5 by volume) as eluent

Sources & evidence

ORD record
ord-81cb2b3da4674d77b708ac61e69b4be4
Source dataset
uspto-grants-1996_10
Patent number
US05563144

Reaction notes

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