Water → tert-butyl 7-bromo-2-(4-methoxybenzyl)-3-oxo-2',3'-dihydro-1'H-spiro[isoindoline-1,4'-pyridine]-1'-carboxylate

HRID 390136Notes

Reaction equation

HRID 390136 reaction equation
[Br:1][C:2]1[C:3](I)=[C:4]([CH:30]=[CH:31][CH:32]=1)[C:5]([N:7]([C:17]1[CH2:22][CH2:21][N:20]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:19][CH:18]=1)[CH2:8][C:9]1[CH:14]=[CH:13][C:12]([O:15][CH3:16])=[CH:11][CH:10]=1)=[O:6].C([O-])([O-])=O.[K+].[K+].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O>CC#N.[Cl-].C([N+](CCCC)(CCCC)CCCC)CCC.CC([O-])=O.CC([O-])=O.[Pd+2]>[Br:1][C:2]1[CH:32]=[CH:31][CH:30]=[C:4]2[C:3]=1[C:17]1([CH:22]=[CH:21][N:20]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:19][CH2:18]1)[N:7]([CH2:8][C:9]1[CH:14]=[CH:13][C:12]([O:15][CH3:16])=[CH:11][CH:10]=1)[C:5]2=[O:6]

Participants

8

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 11776TriphenylphosphineHCID 58295704tert-butyl 4-(3-bromo-2-iodo-N-(4-methoxybenzyl)benzamido)-5,6-dihydropyridine-1(2H)-carboxylate

Product 1

HCID 58295753tert-butyl 7-bromo-2-(4-methoxybenzyl)-3-oxo-2',3'-dihydro-1'H-spiro[isoindoline-1,4'-pyridine]-1'-carboxylateYield 50.1%

Reagents, catalysts & solvents 3

HCID 70681Tetrabutylammonium ChlorideCatalystHCID 167845palladium(II) acetateCatalystHCID 6342AcetonitrileSolvent

Procedure

A solution of tert-butyl 4-(3-bromo-2-iodo-N-(4-methoxybenzyl)benzamido)-5,6-dihydropyridine-1(2H)-carboxylate (30 g, 0.048 mol) in CH3CN (500 mL) was stirred for 0.5 h under nitrogen. K2CO3 (13 g, 0.096 mol), PPh3 (6 g, 20%), tetra-butylammonium chloride (15 g, 0.048 mol) and Pd(OAc)2 (3 g, 0.0048 mol) were added. The resulting mixture was heated to reflux for 12 h. The mixture was poured into water and extracted with EtOAc. The organic layer was dried and concentrated to give the crude product which was purified by column chromatography to afford tert-butyl 7-bromo-2-(4-methoxybenzyl)-3-oxo-2′,3′-dihydro-1′H-spiro[isoindoline-1,4′-pyridine]-1′-carboxylate (12 g, 50%). 1H NMR: (400 MHz, CDCl3): δ=1.51 (s, 9H), 1.73 (m, 2H), 2.83-3.08 (m, 2H), 3.79 (s, 3H), 4.00 (m, 1H), 4.30 (m, 1H), 4.42 (d, 1H), 5.02 (d, 1H), 6.83 (d, 2H), 7.201 (d, 2H), 7.45 (m, 1H), 7.70 (d, 1H), 7.88 (d, 1H).

Workup

  1. temperatureThe resulting mixture was heated
  2. temperatureto reflux for 12 h
  3. extractionextracted with EtOAc
  4. customThe organic layer was dried
  5. concentrationconcentrated
  6. customto give the crude product which
  7. customwas purified by column chromatography

Sources & evidence

ORD record
ord-e61d501e87164d19b02516b56f95ff72
Source dataset
uspto-grants-2013_02
Patent number
US08383629B2

Reaction notes

Loading…