1,2-Dichloroethane → tert-Butyl 5-(5-(3,4-diethoxyphenyl)-1,2,4-oxadiazol-3-yl)isoindoline-2-carboxylate

HRID 710469Notes

Reaction equation

HRID 710469 reaction equation
[CH2:1]([O:3][C:4]1[CH:5]=[C:6]([CH:10]=[CH:11][C:12]=1[O:13][CH2:14][CH3:15])[C:7]([OH:9])=O)[CH3:2].O[NH:17][C:18]([C:20]1[CH:21]=[C:22]2[C:26](=[CH:27][CH:28]=1)[CH2:25][N:24]([C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[CH2:23]2)=[NH:19].C(Cl)CCl>CN(C=O)C.CCOC(C)=O>[CH2:1]([O:3][C:4]1[CH:5]=[C:6]([C:7]2[O:9][N:17]=[C:18]([C:20]3[CH:21]=[C:22]4[C:26](=[CH:27][CH:28]=3)[CH2:25][N:24]([C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[CH2:23]4)[N:19]=2)[CH:10]=[CH:11][C:12]=1[O:13][CH2:14][CH3:15])[CH3:2]

Participants

6

Reactant 3

HCID 111,2-DichloroethaneHCID 794173,4-Diethoxybenzoic acidHCID 178451481HCID 178451481, compound

Product 1

HCID 86661809tert-Butyl 5-(5-(3,4-diethoxyphenyl)-1,2,4-oxadiazol-3-yl)isoindoline-2-carboxylateYield 20.6%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 3,4-diethoxybenzoic acid (0.19 g; 0.904 mmol), a product of Step D (0.25 g; 0.904 mmol) and EDC (0.27 g; 1.4 mmol) in anhydrous DMF (2 ml) was stirred at ˜60° C. for 1 h, then cooled to room temperature and diluted to 20 ml with EtOAc. This was washed with H2O (2×5 ml), brine, dried over anhydrous MgSO4, filtered and filtrate evaporated to dryness. The residue was diluted to 3 ml with anhydrous diglyme and 1M TBAF in THF (0.5 ml) was added and the resulting mixture was stirred at ˜80° C. for 1 h, then solvents were removed in vacuo. The residue was purified by crystallization from MeOH, to give the title compound (0.084 g; 20%) as greyish solid. 1H-NMR (CDCl3) 1.4-1.6 (m, 15H+H2O); 4.14-4.24 (m, 4H); 4.7-4.76 (m, 4H); 6.97 (d, 1H, J=6 Hz); 7.32-7.4 (m, 1H); 7.66 (d, 1H, J=3 Hz); 7.78 (dd, 1H, J=3, 9 Hz); 8.02-8.08 (m, 2H).

Workup

  1. washThis was washed with H2O (2×5 ml), brine
  2. dry with materialdried over anhydrous MgSO4
  3. filtrationfiltered
  4. customfiltrate evaporated to dryness
  5. additionThe residue was diluted to 3 ml with anhydrous diglyme and 1M TBAF in THF (0.5 ml)
  6. additionwas added
  7. customsolvents were removed in vacuo
  8. customThe residue was purified by crystallization from MeOH

Sources & evidence

ORD record
ord-f98aa3ddcb494a7eb53b3bb55670ee16
Source dataset
uspto-grants-2015_11
Patent number
US09181182B2

Reaction notes

Loading…