Acetyl bromide → 6-Methoxy-2-(oxiran-2-ylmethyl)-1-oxo-4-phenyl-1,2-dihydroiso-quinoline-3-carbonitrile

HRID 2358307Notes

Reaction equation

HRID 2358307 reaction equation
O[CH:2]([CH2:25][OH:26])[CH2:3][N:4]1[C:13]([C:14]#[N:15])=[C:12]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([O:22][CH3:23])[CH:10]=2)[C:5]1=[O:24].CC1C=CC(S([O-])(=O)=O)=CC=1.C1C=C[NH+]=CC=1.C(OC)(OC)(OC)C.C(Br)(=O)C.C([O-])([O-])=O.[K+].[K+]>C(Cl)Cl>[CH3:23][O:22][C:9]1[CH:10]=[C:11]2[C:6](=[CH:7][CH:8]=1)[C:5](=[O:24])[N:4]([CH2:3][CH:2]1[CH2:25][O:26]1)[C:13]([C:14]#[N:15])=[C:12]2[C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1

Participants

7

Reactant 5

HCID 10482Acetyl bromideHCID 11430Potassium CarbonateHCID 15050Trimethyl orthoacetateHCID 466102Benzenesulfonic acid, 4-methyl-, compd. with pyridine (1:1)HCID 114053982-(2,3-Dihydroxypropyl)-6-methoxy-1-oxo-4-phenyl-1,2-dihydroisoquinoline-3-carbonitrile

Product 1

HCID 588285196-Methoxy-2-(oxiran-2-ylmethyl)-1-oxo-4-phenyl-1,2-dihydroiso-quinoline-3-carbonitrile

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a room temperature suspension of diol 89 (352 mg, 1 mmol) and PPTS (12 mg, 0.05 mmol) in CH2Cl2 (10 mL) was added trimethyl orthoacetate (0.153 mL, 1.2 mmol). A clear solution resulted within 2 minutes. After stirring at RT for 3.5 h the reaction mixture was concentrated. The residue was dissolved in CH2Cl2 (10 mL) and acetyl bromide (0.089 mL, 1.2 mmol) added. After stirring at RT for 1.5 h the reaction mixture was concentrated. The residue was taken up in 2 mL MeOH (2 mL) to give an orange-brown suspension. K2CO3 (153 mg, 1.1 mol) was added and the resulting mixture stirred at room temperature for 2 h. It was then partitioned between sat NH4Cl and CH2Cl2. The aqueous phase was washed once more with CH2Cl2. The extracts were dried (MgSO4) and concentrated. The product 99 was purified by automated flash chromatography (40-80% EA/Hex).

Workup

  1. customA clear solution resulted within 2 minutes
  2. concentrationwas concentrated
  3. dissolutionThe residue was dissolved in CH2Cl2 (10 mL)
  4. stirringAfter stirring at RT for 1.5 h the reaction mixture
  5. concentrationwas concentrated
  6. customto give an orange-brown suspension
  7. stirringthe resulting mixture stirred at room temperature for 2 h
  8. customIt was then partitioned
  9. washThe aqueous phase was washed once more with CH2Cl2
  10. dry with materialThe extracts were dried (MgSO4)
  11. concentrationconcentrated
  12. customThe product 99 was purified by automated flash chromatography (40-80% EA/Hex)

Sources & evidence

ORD record
ord-f61385f1427d4d46bf7d489f1b620440
Source dataset
uspto-grants-2010_07
Patent number
US07763614B2

Reaction notes

Loading…