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

HRID 390136
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HRID 390136 반응식
[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]
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참가 물질

8

반응물 4

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

생성물 1

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

시약·촉매·용매 3

HCID 70681Tetrabutylammonium Chloride촉매HCID 167845palladium(II) acetate촉매HCID 6342Acetonitrile용매

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-e61d501e87164d19b02516b56f95ff72
출처 데이터셋
uspto-grants-2013_02
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08383629B2

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