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 41450Notes

Reaction equation

HRID 41450 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 D6) (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-16b6e63395da4b8e94991293130e9a5b
Source dataset
uspto-grants-2013_09
Patent number
US08530469B2

Reaction notes

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