1,2-Dichloroethane → 4-[2-(2,4-dihydroxy-5-isopropyl-benzoyl)-2,3-dihydro-1H-isoindole-5-carbonyl]-piperazine-1-carboxylic acid tert-butyl ester

HRID 425214Notes

Reaction equation

HRID 425214 reaction equation
C([O:8][C:9]1[CH:28]=[C:27]([O:29]CC2C=CC=CC=2)[C:26]([CH:37]([CH3:39])[CH3:38])=[CH:25][C:10]=1[C:11]([N:13]1[CH2:21][C:20]2[C:15](=[CH:16][CH:17]=[C:18]([C:22](O)=[O:23])[CH:19]=2)[CH2:14]1)=[O:12])C1C=CC=CC=1.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.[C:54]([N:61]1[CH2:66][CH2:65][NH:64][CH2:63][CH2:62]1)([O:56][C:57]([CH3:60])([CH3:59])[CH3:58])=[O:55]>CN(C=O)C>[C:57]([O:56][C:54]([N:61]1[CH2:62][CH2:63][N:64]([C:22]([C:18]2[CH:19]=[C:20]3[C:15](=[CH:16][CH:17]=2)[CH2:14][N:13]([C:11](=[O:12])[C:10]2[CH:25]=[C:26]([CH:37]([CH3:39])[CH3:38])[C:27]([OH:29])=[CH:28][C:9]=2[OH:8])[CH2:21]3)=[O:23])[CH2:65][CH2:66]1)=[O:55])([CH3:60])([CH3:59])[CH3:58]

Participants

6

Reactant 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 143452tert-Butyl piperazine-1-carboxylateHCID 590070032-(2,4-bis-benzyloxy-5-isopropyl-benzoyl)-2,3-dihydro-1H-isoindole-5-carboxylic acid

Product 1

HCID 666726574-[2-(2,4-dihydroxy-5-isopropyl-benzoyl)-2,3-dihydro-1H-isoindole-5-carbonyl]-piperazine-1-carboxylic acid tert-butyl esterYield 102.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 2-(2,4-bis-benzyloxy-5-isopropyl-benzoyl)-2,3-dihydro-1H-isoindole-5-carboxylic acid (Preparation D10) (0.5 g, 0.96 mmol), EDC (0.22 g, 1.15 mmol), HOBT (0.196 g, 1.15 mmol) and BOC piperazine (0.117 ml, 1.06 mmol) in DMF (10 ml) was stirred at room temperature for 48 hours, then evaporated under vacuum. The crude material was dissolved in ethyl acetate and extracted twice with saturated NaHCO3, organics washed with brine, dried (MgSO4), filtered then evaporated under vacuum and purified by flash column chromatography (80% EtOAc-P.E. as eluant) to give 0.5 g of 4-[2-(2,4-dihydroxy-5-isopropyl-benzoyl)-2,3-dihydro-1H-isoindole-5-carbonyl]-piperazine-1-carboxylic acid tert-butyl ester. MS: [M+H]+ 688.

Workup

  1. customevaporated under vacuum
  2. dissolutionThe crude material was dissolved in ethyl acetate
  3. extractionextracted twice with saturated NaHCO3
  4. washorganics washed with brine
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. customthen evaporated under vacuum
  8. custompurified by flash column chromatography (80% EtOAc-P.E. as eluant)

Sources & evidence

ORD record
ord-5bd6be5f02b241cfa054f5a316d9d6e7
Source dataset
uspto-grants-2012_01
Patent number
US08106057B2

Reaction notes

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