1,3-Bis(diphenylphosphino)propane → 2-Tert-butyl 5-methyl isoindoline-2,5-dicarboxylate

HRID 1726435Notes

Reaction equation

HRID 1726435 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:16][C:15]2[C:10](=[CH:11][CH:12]=[C:13](Br)[CH:14]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C1C=CC(P(C2C=CC=CC=2)CCCP(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CO.CS(C)=O.C[CH2:54][O:55][C:56](C)=[O:57].CCCCCC>CC([O-])=O.CC([O-])=O.[Pd+2]>[CH3:54][O:55][C:56]([C:13]1[CH:14]=[C:15]2[C:10](=[CH:11][CH:12]=1)[CH2:9][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[CH2:16]2)=[O:57]

Participants

6

Reactant 4

HCID 812191,3-Bis(diphenylphosphino)propaneHCID 16102683N-Boc-5-bromoisoindolineHCID 21226206Ethyl acetate hexaneHCID 22036561Dimethyl sulfoxide methanol

Product 1

HCID 179863022-Tert-butyl 5-methyl isoindoline-2,5-dicarboxylateYield 81%

Reagents, catalysts & solvents 1

HCID 167845palladium(II) acetateCatalyst

Conditions

Temperature
80 °C

Procedure

A mixture of 5-bromo-1,3-dihydro-isoindole-2-carboxylic acid tert-butyl ester (200 mg, 0.67 mmol), Pd(OAc)2 (30 mg, 0.2 equiv), DPPP (55 mg, 0.2 equiv), TEA (0.93 mL, 10 equiv) and MeOH:DMSO (1:1, 4 mL) was stirred for 16 h under CO (balloon) at 80° C. LC-MS and TLC (20% EtOAc-Hexane) showed completion of the reaction. The Reaction mixture was concentrated to remove MeOH and diluted with EtOAc (10 mL), and washed with water (2×25 mL). The organic layer was dried (Na2SO4), concentrated and purified by silica gel column chromatography (eluent=20% EtOAc-Hexane), giving pure 1,3-dihydro-isoindole-2,5-dicarboxylic acid 2-tert-butyl ester 5-methyl ester (150 mg, 81%). MS (APCI+): m/z 178.1 (MH+−Boc).

Workup

  1. customcompletion of the reaction
  2. concentrationThe Reaction mixture was concentrated
  3. customto remove MeOH
  4. additiondiluted with EtOAc (10 mL)
  5. washwashed with water (2×25 mL)
  6. dry with materialThe organic layer was dried (Na2SO4)
  7. concentrationconcentrated
  8. custompurified by silica gel column chromatography (eluent=20% EtOAc-Hexane)

Sources & evidence

ORD record
ord-4ec37d33dd3243b082fd7b7457af1d25
Source dataset
uspto-grants-2009_02
Patent number
US07491794B2

Reaction notes

Loading…