4-Bromoanisole → 1-(3-Bromophenyl)-1-(4-methoxyphenyl)-1H-isoindol-3-amine

HRID 2264726Notes

Reaction equation

HRID 2264726 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[CH:4][CH:3]=1.C([Li])CCC.[Br:15][C:16]1[CH:17]=[C:18]([C:22]([C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=2[C:36]#[N:37])=[N:23]S(C(C)(C)C)=O)[CH:19]=[CH:20][CH:21]=1>O1CCCC1>[Br:15][C:16]1[CH:17]=[C:18]([C:22]2([C:2]3[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[CH:4][CH:3]=3)[C:30]3[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=3)[C:36]([NH2:37])=[N:23]2)[CH:19]=[CH:20][CH:21]=1

Participants

5

Reactant 3

HCID 77304-BromoanisoleHCID 72335434N-[(3-bromophenyl)(2-cyanophenyl)methylene]-2-methylpropane-2-sulfinamideHCID 178418339Butyllithium

Product 1

HCID 248749461-(3-Bromophenyl)-1-(4-methoxyphenyl)-1H-isoindol-3-amineYield 59.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a −78° C. solution of 4-bromoanisole (0.45 mL, 3.6 mmol) in tetrahydrofuran (15 mL) was n-butyllithium (2.5 M in hexane, 1.3 mL, 3.3 mmol) added, after 0.5 h a solution of N-[(3-bromophenyl)(2-cyanophenyl)methylene]-2-methylpropane-2-sulfinamide (Scheme #5, N) (1.2 g, 3.0 mmol) in tetrahydrofuran (5 mL) was added. The reaction mixture was stirred at −78° C. for 3 h and then quenched by addition of water. Ethyl acetate was added and the mixture was washed with water and brine, dried over magnesium sulfate and concentrated. The residue was dissolved in methanol (25 mL) and treated with hydrochloric acid (2 M in diethyl ether, 3.0 mL, 6.0 mml) over night. The reaction mixture was concentrated and then partitioned between aqueous saturated sodium bicarbonate and chloroform, the organic phase was dried over magnesium sulfate and concentrated. Purification by column chromatography using a gradient of methanol in dichloromethane gave the title compound (0.70 g, 59%). 1H NMR (CDCl3) δ 7.57-7.48 (m, 3 H), 7.47-7.41 (m, 1 H), 7.39-7.32 (m, 2 H), 7.32-7.28 (m, 1 H), 7.26-7.20 (m, 2 H), 7.10 (t, J=7.83 Hz, 1 H), 6.83-6.77 (m, 2 H), 5.86 (br s, 2 H), 3.75 (s, 3 H); MS (AP) m/z 393, 395 [M+1]+.

Workup

  1. customTo a −78° C.
  2. additionwas added
  3. customquenched by addition of water
  4. additionEthyl acetate was added
  5. washthe mixture was washed with water and brine
  6. dry with materialdried over magnesium sulfate
  7. concentrationconcentrated
  8. dissolutionThe residue was dissolved in methanol (25 mL)
  9. additiontreated with hydrochloric acid (2 M in diethyl ether, 3.0 mL, 6.0 mml) over night
  10. concentrationThe reaction mixture was concentrated
  11. custompartitioned between aqueous saturated sodium bicarbonate and chloroform
  12. dry with materialthe organic phase was dried over magnesium sulfate
  13. concentrationconcentrated
  14. customPurification by column chromatography

Sources & evidence

ORD record
ord-24e93e1db6324c279564bd6ea03dd634
Source dataset
uspto-grants-2010_12
Patent number
US07855213B2

Reaction notes

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