Potassium Carbonate → 4-{4-[2-(2,4-bis-benzyloxy-5-isopropenyl-benzoyl)-2,3-dihydro-1H-isoindol-5-yl]phenyl}piperazine-1-carboxylic acid tert-butyl ester

HRID 424102Notes

Reaction equation

HRID 424102 reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[C:13]([O:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[C:12]([C:23]([CH3:25])=[CH2:24])=[CH:11][C:10]=1[C:26]([N:28]1[CH2:36][C:35]2[C:30](=[CH:31][CH:32]=[C:33](Br)[CH:34]=2)[CH2:29]1)=[O:27])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:38]([O:42][C:43]([N:45]1[CH2:50][CH2:49][N:48]([C:51]2[CH:56]=[CH:55][C:54](B3OC(C)(C)C(C)(C)O3)=[CH:53][CH:52]=2)[CH2:47][CH2:46]1)=[O:44])([CH3:41])([CH3:40])[CH3:39].C(=O)([O-])[O-].[K+].[K+]>C1(C)C=CC=CC=1.O.C(O)C.CCOC(C)=O.CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C>[C:38]([O:42][C:43]([N:45]1[CH2:50][CH2:49][N:48]([C:51]2[CH:56]=[CH:55][C:54]([C:33]3[CH:34]=[C:35]4[C:30](=[CH:31][CH:32]=3)[CH2:29][N:28]([C:26](=[O:27])[C:10]3[CH:11]=[C:12]([C:23]([CH3:25])=[CH2:24])[C:13]([O:15][CH2:16][C:17]5[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=5)=[CH:14][C:9]=3[O:8][CH2:1][C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)[CH2:36]4)=[CH:53][CH:52]=2)[CH2:47][CH2:46]1)=[O:44])([CH3:41])([CH3:39])[CH3:40]

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 27955144-(4-tert-Butoxycarbonylpiperazinyl)phenylboronic acid, pinacol esterHCID 46915776(2,4-Bis-benzyloxy-5-isopropenyl-phenyl)-(5-bromo-1,3-dihydro-isoindol-2-yl)-methanone

Product 1

HCID 666725624-{4-[2-(2,4-bis-benzyloxy-5-isopropenyl-benzoyl)-2,3-dihydro-1H-isoindol-5-yl]phenyl}piperazine-1-carboxylic acid tert-butyl esterYield 26.9%

Reagents, catalysts & solvents 3

HCID 178418851HCID 178418851, compoundCatalystHCID 8857Ethyl AcetateSolventHCID 86587398Ethanol toluene waterSolvent

Conditions

Temperature
135 °C

Procedure

A mixture of (2,4-bis-benzyloxy-5-isopropenyl-phenyl)-(5-bromo-1,3-dihydro-isoindol-2-yl)-methanone (240 mg, 0.43 mmol), t-butyl-4-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]piperazine carboxylate (210 mg, 1.25 equiv.), bis(tri-t-butylphosphine)palladium(0) (12.5 mg, 2.5 mol %) and potassium carbonate (350 mg, 6 equiv.) in toluene/water/ethanol (1 ml: 1 ml: 4 ml) was heated at 135° C. for 30 minutes in a CEM explorer microwave synthesiser. The reaction mixture was diluted with EtOAc, washed with saturated NaHCO3, dried (MgSO4) and evaporated. Purification by flash column chromatography (Biotage SP4-25S, 25 ml/min) eluting with 1:3 then 1:1 EtOAc/P.E. Evaporation of product containing fractions gave 85 mg of 4-{4-[2-(2,4-bis-benzyloxy-5-isopropenyl-benzoyl)-2,3-dihydro-1H-isoindol-5-yl]-phenyl}piperazine-1-carboxylic acid tert-butyl ester. MS: [M+H]+ 736.

Workup

  1. washwashed with saturated NaHCO3
  2. dry with materialdried (MgSO4)
  3. customevaporated
  4. customPurification by flash column chromatography (Biotage SP4-25S, 25 ml/min)
  5. washeluting with 1:3
  6. customEvaporation of product
  7. additioncontaining fractions

Sources & evidence

ORD record
ord-5ff516e8813045cf89c5be6dd01e4f73
Source dataset
uspto-grants-2012_01
Patent number
US08101648B2

Reaction notes

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