Dimethyl Sulfoxide → 3-Chloroisoquinoline-6-carboxylic acid
Reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH:8]=[N:7][C:6]([Cl:12])=[CH:5]2.C[Si](C)(C)C[CH2:16][OH:17].CS(C)=[O:22]>CN(C=O)C.CCOC(C)=O.CC([O-])=O.CC([O-])=O.[Pd+2].C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[Cl:12][C:6]1[N:7]=[CH:8][C:9]2[C:4]([CH:5]=1)=[CH:3][C:2]([C:16]([OH:17])=[O:22])=[CH:11][CH:10]=2Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 4
Conditions
- Temperature
- 120 °C
Procedure
A suspension of 6-bromo-3-chloroisoquinoline (93.5 mg, 0.386 mmol), 2-(trimethylsilyl)-ethanol (456 mg, 3.856 mmol), Pd(OAc)2 (8.7 mg, 0.039 mmol), 1,1′-Bis(diphenyl-phosphino)ferrocene (45.1 mg, 0.077 mmol) and DMSO (27 uL, 0.386 mmol) in DMF (6 mL) was placed in a microwave tube (15 mL). The reaction was saturated with CO gas for 10 minutes before the tube was sealed and stirred at 120° C. under microwave irradiation for 10 hours. The reaction mixture was diluted with EtOAc and filtered. 2M NaOH (0.5 mL) was added to the filtrate and extracted with brine. The combined aqueous layers were washed with EtOAc and acidified carefully with drops of concentrated HCl to pH=3. The resulting cloudy solution was extracted with EtOAc, dried over sodium sulphate and concentrated in vacuo to afford the title compound as light brown solid (21 mg, 26%).
Workup
- customwas placed in a microwave tube
- customwas sealed
- filtrationfiltered
- addition2M NaOH (0.5 mL) was added to the filtrate
- extractionextracted with brine
- washThe combined aqueous layers were washed with EtOAc
- extractionThe resulting cloudy solution was extracted with EtOAc
- dry with materialdried over sodium sulphate
- concentrationconcentrated in vacuo
Sources & evidence
- ORD record
- ord-703c7d1aaaa14af390876e72ec2df744
- Source dataset
- uspto-grants-2016_05
- Patent number
- US09334286B2
Reaction notes
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