Thionyl Chloride → 2,4-bisbenzyloxy-N-butyl-5-(5-bromo-1,3-dihydroisoindole-2-carbonyl)-N-methylbenzamide

HRID 1927705Notes

Reaction equation

HRID 1927705 reaction equation
S(Cl)(Cl)=O.[CH3:5][N:6]([C:11]([C:13]1[C:14]([O:30][CH2:31][C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)=[CH:15][C:16]([O:22][CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)=[C:17]([CH:21]=1)[C:18](O)=[O:19])=[O:12])[CH2:7][CH2:8][CH2:9][CH3:10].[Br:38][C:39]1[CH:40]=[C:41]2[C:45](=[CH:46][CH:47]=1)[CH2:44][NH:43][CH2:42]2.C(N(C(C)C)C(C)C)C>C1COCC1.ClCCl.C1(C)C=CC=CC=1>[CH2:31]([O:30][C:14]1[CH:15]=[C:16]([O:22][CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[C:17]([C:18]([N:43]2[CH2:42][C:41]3[C:45](=[CH:46][CH:47]=[C:39]([Br:38])[CH:40]=3)[CH2:44]2)=[O:19])=[CH:21][C:13]=1[C:11]([N:6]([CH2:7][CH2:8][CH2:9][CH3:10])[CH3:5])=[O:12])[C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1

Participants

8

Reactant 4

HCID 24386Thionyl ChlorideHCID 81531DiisopropylethylamineHCID 147958715-BromoisoindolineHCID 596140605-[(N-Methyl-N-butylamino)carbonyl]-2,4-bisbenzyloxybenzoic acid

Product 1

HCID 596141252,4-bisbenzyloxy-N-butyl-5-(5-bromo-1,3-dihydroisoindole-2-carbonyl)-N-methylbenzamideYield 42%

Reagents, catalysts & solvents 3

HCID 1140TolueneSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
22 °C

Procedure

652.9 μl (9 mmol) of thionyl chloride are added to a suspension of 2.06 g (4.6 mmol) of 2,4-bisbenzyloxy-5-[(N-methyl-N-butylamino)carbonyl]benzoic acid (5) in 20 ml of THF (dry), and the mixture is stirred for 15 min at 22° C. 10 ml of toluene are subsequently added, and the mixture is evaporated to dryness in vacuo at 40° C. The residue is dissolved in 20 ml of THF and added to a suspension of 923 mg (4.661 mmol) of 5-bromo-2,3-dihydro-1H-isoindole (13) in 30 ml of dichloromethane, 5 ml of THF and 1.7 ml (10 mmol) of N-ethyldiisopropylamine. After 2 h at 22° C., the mixture is evaporated and chromatographed over an RP18 column. Evaporation to dryness in vacuo gives 1.2 g (42%) of 2,4-bisbenzyloxy-N-butyl-5-(5-bromo-1,3-dihydroisoindole-2-carbonyl)-N-methylbenzamide (“A16a”), MW 627.6; Rt 2.478 min.

Workup

  1. customthe mixture is evaporated to dryness in vacuo at 40° C
  2. dissolutionThe residue is dissolved in 20 ml of THF
  3. waitAfter 2 h at 22° C.
  4. customthe mixture is evaporated
  5. customchromatographed over an RP18 column
  6. customEvaporation to dryness in vacuo

Sources & evidence

ORD record
ord-9bc1b679546c402d989e59c56b857acf
Source dataset
uspto-grants-2012_05
Patent number
US08183279B2

Reaction notes

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