Trifluoroacetic acid → 2-((6-Bromopyridin-2-yl)methyl)isoindoline-1,3-dione

HRID 2387703Notes

Reaction equation

HRID 2387703 reaction equation
[Br:1][C:2]1[N:7]=[C:6]([CH2:8]O)[CH:5]=[CH:4][CH:3]=1.[C:10]1(=[O:20])[NH:14][C:13](=[O:15])[C:12]2=[CH:16][CH:17]=[CH:18][CH:19]=[C:11]12.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O.C(O)(C(F)(F)F)=O>O1CCCC1.O.CO>[Br:1][C:2]1[N:7]=[C:6]([CH2:8][N:14]2[C:10](=[O:20])[C:11]3[C:12](=[CH:16][CH:17]=[CH:18][CH:19]=3)[C:13]2=[O:15])[CH:5]=[CH:4][CH:3]=1

Participants

9

Reactant 5

HCID 6422Trifluoroacetic acid2×HCID 6809PhthalimideHCID 11776TriphenylphosphineHCID 730421,1'-(Azodicarbonyl)dipiperidineHCID 3517811(6-Bromopyridin-2-yl)methanol

Product 1

HCID 221764462-((6-Bromopyridin-2-yl)methyl)isoindoline-1,3-dione

Reagents, catalysts & solvents 3

HCID 887MethanolSolvent3×HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of commercially available (6-bromopyridin-2-yl)methanol (20.0 g, 0.106 mol), phthalimide (20.4 g, 0.138 mol), and triphenylphosphine (36.2 g, 0.138 mol), and 1,1′-(azodicarbonyl)-dipiperidine (34.8 g, 0.138 mol) in anhydrous tetrahydrofuran (1 L) was stirred at room temperature overnight. The precipitate was collected by vacuum filtration and washed with tetrahydrofuran. The filtrate was concentrated under reduced pressure, and the solid residue was triturated with methanol with sonication. A214.1 was collected by vacuum filtration and was dried well to give 24.1 g as a white solid. The filtrate still contained significant product which could be isolated as a second crop with methanol trituration. The compound had an HPLC retention time=2.32 min. (Column: Chromolith SpeedROD 4.6×50 mm−4 min.; Solvent A=10% MeOH, 90% H2O, and 0.1% TFA; Solvent B=90% MeOH, 10% H2O, and 0.1% TFA) and a LC/MS M+1=317.15 and 319.15.

Workup

  1. filtrationThe precipitate was collected by vacuum filtration
  2. washwashed with tetrahydrofuran
  3. concentrationThe filtrate was concentrated under reduced pressure
  4. customthe solid residue was triturated with methanol with sonication
  5. filtrationA214.1 was collected by vacuum filtration
  6. customwas dried well
  7. customto give 24.1 g as a white solid

Sources & evidence

ORD record
ord-ff3a65e5bd314c6baeff4d7e3cbe2ff2
Source dataset
uspto-grants-2012_09
Patent number
US08268855B2

Reaction notes

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