Phthalimide → 2-((5-Chloro-6-(2,2-difluoroethoxy)pyridin-3-yl)methyl)isoindoline-1,3-dione

HRID 715364Notes

Reaction equation

HRID 715364 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH2:13]O)[CH:5]=[N:6][C:7]=1[O:8][CH2:9][CH:10]([F:12])[F:11].[C:15]1(=[O:25])[NH:19][C:18](=[O:20])[C:17]2=[CH:21][CH:22]=[CH:23][CH:24]=[C:16]12.N(C(OC(C)(C)C)=O)=NC(OC(C)(C)C)=O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([CH2:13][N:19]2[C:15](=[O:25])[C:16]3[C:17](=[CH:21][CH:22]=[CH:23][CH:24]=3)[C:18]2=[O:20])[CH:5]=[N:6][C:7]=1[O:8][CH2:9][CH:10]([F:11])[F:12]

Participants

6

Reactant 4

HCID 6809PhthalimideHCID 11776TriphenylphosphineHCID 97268Di-tert-butyl azodicarboxylateHCID 82006081(5-Chloro-6-(2,2-difluoroethoxy)pyridin-3-yl)methanol

Product 1

HCID 874266212-((5-Chloro-6-(2,2-difluoroethoxy)pyridin-3-yl)methyl)isoindoline-1,3-dioneYield 93%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of (5-chloro-6-(2,2-difluoroethoxy)pyridin-3-yl)methanol (0.87 g, 3.88 mmol, Step-3), phthalimide (0.63 g, 4.26 mmol), di-tert-butyl azodicarboxylate (2.11 mL, 4.65 mmol, ca. 2.2 mol/L in toluene) and triphenylphosphine (1.53 g, 5.81 mmol) in THF (26 mL) is stirred at rt for 2 hours. The reaction mixture is concentrated in vacuo. The residue is purified by column chromatography on silica gel eluting with n-hexane/EtOAc (10:1 to 3:1) to give 1.27 g (93% yield) of the title compound as white solid.

Workup

  1. concentrationThe reaction mixture is concentrated in vacuo
  2. customThe residue is purified by column chromatography on silica gel eluting with n-hexane/EtOAc (10:1 to 3:1)

Sources & evidence

ORD record
ord-529862672f25454abcf886c851a6e913
Source dataset
uspto-grants-2015_11
Patent number
US09187475B2

Reaction notes

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