1-Bromo-2-methylpropane → HCID 18975664, compound

HRID 2393112Notes

Reaction equation

HRID 2393112 reaction equation
C([Li])CCC.C(NC(C)C)(C)C.[CH:13]1([C:17]2[C:26]3[C:21](=[CH:22][CH:23]=[C:24]([O:27][CH3:28])[CH:25]=3)[CH2:20][CH2:19][N:18]=2)[CH2:16][CH2:15][CH2:14]1.Br[CH2:30][CH:31]([CH3:33])[CH3:32]>O1CCCC1>[CH3:28][O:27][C:24]1[CH:25]=[C:26]2[C:21]([CH2:20][CH2:19][N:18]=[C:17]2[C:13]2([CH2:30][CH:31]([CH3:33])[CH3:32])[CH2:14][CH2:15][CH2:16]2)=[CH:22][CH:23]=1

Participants

6

Reactant 4

HCID 65551-Bromo-2-methylpropaneHCID 7912DiisopropylamineHCID 18975659HCID 18975659, compoundHCID 178418339Butyllithium

Product 1

HCID 18975664HCID 18975664, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-23 °C

Procedure

n-Butyllithium (2.83 ml, 1.8M in hexanes) was added dropwise to a solution of diisopropylamine (0.71 ml) in dry tetrahydrofuran (5 ml) at ambient temperature. After 15 minutes the solution was cooled to -23° C. and treated slowly with a solution of 1-cyclobutyl-7-methoxy-3,4-dihydroisoquinoline (1 g) in tetrahydrofuran (11 ml). The dark green solution was stirred for 30 minutes, further cooled to -78° C. and treated with 1-bromo-2-methylpropane (5.1 ml). After 1 hour at -78° C. the mixture was allowed to warm to ambient temperature, then heated under reflux for 1 hour. The mixture was poured onto water, acidified, and washed with ether. The aqueous phase was then basified by addition of aqueous sodium hydroxide solution and extracted with ethyl acetate. The solvent was removed in vacuo to yield an orange gum which was purified by flash chromatography over silica gel using a 1:4 mixture of ethyl acetate and light petroleum ether as eluant to give 7-methoxy-1-[1-(2-methylpropyl)cyclobutyl]-3,4-dihydroisoquinoline as an oil (0.85 g).

Workup

  1. temperaturefurther cooled to -78° C.
  2. waitAfter 1 hour at -78° C. the mixture was allowed
  3. temperatureto warm to ambient temperature
  4. temperatureheated
  5. temperatureunder reflux for 1 hour
  6. additionThe mixture was poured onto water
  7. washwashed with ether
  8. additionThe aqueous phase was then basified by addition of aqueous sodium hydroxide solution
  9. extractionextracted with ethyl acetate
  10. customThe solvent was removed in vacuo
  11. customto yield an orange gum which
  12. customwas purified by flash chromatography over silica gel using
  13. additiona 1:4 mixture of ethyl acetate and light petroleum ether as eluant

Sources & evidence

ORD record
ord-0e2daf3fef7d4a94bffdfea4c8262521
Source dataset
uspto-grants-1998_09
Patent number
US05804586

Reaction notes

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