Tetramethyltin → 3-Isoquinolinecarboxylic acid, 4-hydroxy-1-methyl-7-phenoxy-, methyl ester

HRID 1481116

Reaction equation

HRID 1481116 reaction equation
[CH3:1][O:2][C:3]([C:5]1[N:6]=[C:7](Br)[C:8]2[C:13]([C:14]=1[OH:15])=[CH:12][CH:11]=[C:10]([O:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[CH:9]=2)=[O:4].[Sn](C)(C)(C)[CH3:25]>CN1CCCC1=O>[CH3:1][O:2][C:3]([C:5]1[N:6]=[C:7]([CH3:25])[C:8]2[C:13]([C:14]=1[OH:15])=[CH:12][CH:11]=[C:10]([O:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[CH:9]=2)=[O:4]

Participants

4

Reactant 2

HCID 11661TetramethyltinHCID 89813003Methyl 1-bromo-4-hydroxy-7-phenoxyisoquinoline-3-carboxylate

Product 1

HCID 712448953-Isoquinolinecarboxylic acid, 4-hydroxy-1-methyl-7-phenoxy-, methyl esterYield 58.2%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

To a mixture of 1-bromo-4-hydroxy-7-phenoxy-isoquinoline-3-carboxylic acid methyl ester (500 mg, 1.34 mmol) in N-methylpyrrolidone (NMP) (7 mL) was added SnMe4 (358 mg, 2.0 mmol) and resin-bound-Pd(PPh3)2Cl2 (Sigma-Aldrich) (1-2 mmol/g) (40 mg, ca. 0.03 mmol). The resultant mixture was stirred in a 130° C. oil bath for 3 h. Reaction mixture was filtered and rinsed with NMP (1 mL). Filtrate was poured into water (120 mL) and stirred at room temperature until good precipitate formed. Solid was collected and rinsed with water (100 mL) and then hexanes (50 mL). Solid was dried and purified by silica gel chromatography, eluting with 2-50% EtOAc/hexanes, to provide the title compound 240 mg (0.78 mmol) in 58% yield. 1H NMR (200 MHz) CDCl3, δ in ppm: 11.68 (s, 1H), 8.37 (d, J=9.3 Hz, 1H), 7.48-7.08 (m, 7H), 4.07 (s, 3H), 2.75 (s, 3H).

Workup

  1. customReaction mixture
  2. filtrationwas filtered
  3. washrinsed with NMP (1 mL)
  4. additionFiltrate was poured into water (120 mL)
  5. customformed
  6. customSolid was collected
  7. washrinsed with water (100 mL)
  8. customSolid was dried
  9. custompurified by silica gel chromatography
  10. washeluting with 2-50% EtOAc/hexanes

Sources & evidence

ORD record
ord-962b33ddd8fe4c9894890c285bb31bdf
Source dataset
uspto-grants-2016_08
Patent number
US09409892B2

Linked notes

Loading…