1-Bromo-3-cyclopropylbenzene → (4-Tert-butylbenzyl)-[2-(3-cyclopropylphenyl)-ethyl]-amine

HRID 19788

Reaction equation

HRID 19788 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:8]2[CH2:10][CH2:9]2)[CH:5]=[CH:6][CH:7]=1.[Li]CCCC.[C:16]([C:20]1[CH:33]=[CH:32][C:23]([CH2:24][N:25]2[CH2:29][CH2:28]OS2(=O)=O)=[CH:22][CH:21]=1)([CH3:19])([CH3:18])[CH3:17]>C1COCC1>[C:16]([C:20]1[CH:21]=[CH:22][C:23]([CH2:24][NH:25][CH2:29][CH2:28][C:2]2[CH:7]=[CH:6][CH:5]=[C:4]([CH:8]3[CH2:10][CH2:9]3)[CH:3]=2)=[CH:32][CH:33]=1)([CH3:18])([CH3:17])[CH3:19]

Participants

5

Reactant 3

HCID 32826721-Bromo-3-cyclopropylbenzeneHCID 866139913-(4-Tert-butylbenzyl)-[1,2,3]oxathiazolidine 2,2-dioxideHCID 178418339Butyllithium

Product 1

HCID 68558075(4-Tert-butylbenzyl)-[2-(3-cyclopropylphenyl)-ethyl]-amineYield 58%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a solution of m-bromophenylcyclopropane (synthesized as described in J. Org. Chem. 1976, 41, 2262-2266) (100 mg, 0.51 mmol) in dry THF (3 ml) at −78° C. was added nBuLi (317 μl, 1.6M solution in hexane, 0.51 mmol) dropwise. The reaction mixture was stirred at −78° C. for 10 min and then a solution of 3-(4-tert-butylbenzyl)-[1,2,3]oxathiazolidine 2,2-dioxide (109 mg, 0.41 mmol) in THF (1 ml) was added dropwise. The reaction mixture was warmed to 0° C. over 3 hours and then quenched with 5 ml 20% (v/v) H2SO4. The reaction mixture was warmed to 60° C. overnight and then cooled to RT and poured into water. The aqueous phase was made basic with 1N NaOH and then extracted with ethyl acetate. The organic layers were combined, washed with brine, dried over MgSO4, filtered and concentrated in vacuo to give a crude residue which was purified by flash column chromatography to give (4-tert-butylbenzyl)-[2-(3-cyclopropylphenyl)-ethyl]-amine (72 mg, 58%) as a colorless oil. MS (ISP) 308.4 (M+H)+.

Workup

  1. temperatureThe reaction mixture was warmed to 0° C. over 3 hours
  2. customquenched with 5 ml 20% (v/v) H2SO4
  3. temperatureThe reaction mixture was warmed to 60° C. overnight
  4. temperaturecooled to RT
  5. additionpoured into water
  6. extractionextracted with ethyl acetate
  7. washwashed with brine
  8. dry with materialdried over MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customto give a crude residue which
  12. customwas purified by flash column chromatography

Sources & evidence

ORD record
ord-2c0dd3f7a9824522b6e400300d26c854
Source dataset
uspto-grants-2010_06
Patent number
US07745477B2

Linked notes

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