Hydrochloric Acid → (R)-2-(1-hydroxypropan-2-yl)-6-methyl-5-nitroisoquinolin-1(2H)-one

HRID 418485Notes

Reaction equation

HRID 418485 reaction equation
[CH3:1]C(C)([O-])C.[K+].[OH:7][CH2:8][C@H:9]([N:11]1[CH:20]=[CH:19][C:18]2[C:13](=[CH:14][CH:15]=[CH:16][C:17]=2[N+:21]([O-:23])=[O:22])[C:12]1=[O:24])[CH3:10].Cl.FC(F)(F)C(O)=O.C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O.C(OCC)(=O)C.O.C(O)(=O)C>[OH:7][CH2:8][C@H:9]([N:11]1[CH:20]=[CH:19][C:18]2[C:13](=[CH:14][CH:15]=[C:16]([CH3:1])[C:17]=2[N+:21]([O-:23])=[O:22])[C:12]1=[O:24])[CH3:10]

Participants

10

Reactant 5

HCID 313Hydrochloric AcidHCID 6422Trifluoroacetic acidHCID 11430Potassium CarbonateHCID 23665647Potassium tert-butoxideHCID 59515694(R)-2-(1-hydroxypropan-2-yl)-5-nitroisoquinolin-1(2H)-one

Product 1

HCID 59515931(R)-2-(1-hydroxypropan-2-yl)-6-methyl-5-nitroisoquinolin-1(2H)-one

Reagents, catalysts & solvents 4

HCID 176Acetic AcidSolventHCID 962WaterSolventHCID 6228DimethylformamideSolvent3×HCID 8857Ethyl AcetateSolvent

Procedure

A round bottom flask was charged with potassium tert-Butoxide (3.62 g, 0.0322 mol) and N,N-dimethylformamide (100 mL, 1 mol) and a solution of acetic acid, chloro-, 1,1-dimethylethyl ester (1.3 mL, 0.0089 mol) and (R)-2-(1-hydroxypropan-2-yl)-5-nitroisoquinolin-1(2H)-one (2.00 g, 0.00806 mol) in N,N-dimethylformamide (20 mL, 0.2 mol) was added at −20° C. dropwise over a period of 8 minutes and the reaction was stirred for an additional 45 minutes at the same temperature. The reaction mixture was poured onto 4 ml of hydrochloric acid and 80 mL of water, and extracted with dichloromethane, washed with brine and dried. the solvent was removed under reduced pressureunder reduced pressure and the residue was used in the next reaction without purification (two isomers in the ratio of 3:1). The residue was treated with trifluoroacetic acid (10 mL, 0.1 mol) for 30 minutes and the trifluoroacetic acid was removed under reduced pressure. The residue was stirred with potassium carbonate (2.2 g, 0.016 mol) in N,N-dimethylformamide (10 mL) at 50° C. for 1 hour. The reaction mixture was cooled and diluted with ethyl acetate (400 mL), washed with 6 N hydrochloric acid (50 mL×4) and the brine (50 mL×2), and dried. The volatiles were removed under reduced pressure and the residue was purified by column chromatography to afford the product as a yellow solid.

Workup

  1. extractionextracted with dichloromethane
  2. washwashed with brine
  3. customdried
  4. customthe solvent was removed
  5. customthe residue was used in the next reaction without purification (two isomers in the ratio of 3:1)
  6. customthe trifluoroacetic acid was removed under reduced pressure
  7. temperatureThe reaction mixture was cooled
  8. washwashed with 6 N hydrochloric acid (50 mL×4)
  9. dry with materialthe brine (50 mL×2), and dried
  10. customThe volatiles were removed under reduced pressure
  11. customthe residue was purified by column chromatography

Sources & evidence

ORD record
ord-1fbb4ef6f7234873aef14a2b0562196a
Source dataset
uspto-grants-2012_01
Patent number
US08093265B2

Reaction notes

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