Methyl iodide → HCID 10517541, compound

HRID 1938428Notes

Reaction equation

HRID 1938428 reaction equation
[C:1]([O:5][C:6]([N:8]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[C:11](=[O:18])[CH2:10][C:9]1([CH3:20])[CH3:19])=[O:7])([CH3:4])([CH3:3])[CH3:2].I[CH3:22].[H-].[Na+]>CN(C=O)C>[C:1]([O:5][C:6]([N:8]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[C:11](=[O:18])[CH:10]([CH3:22])[C:9]1([CH3:20])[CH3:19])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 10612446tert-Butyl 2,2-dimethyl-4-oxo-3,4-dihydroquinoline-1(2H)-carboxylate

Product 1

HCID 10517541HCID 10517541, compoundYield 86.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 1-tert-butoxycarbonyl-1,2,3,4-tetrahydro-2,2-dimethyl-4-quinolinone (0.10 g, 0.36 mmol) and iodomethane (0.50 mL, 8.0 mmol) in DMF (4 mL) was added NaH (60% in mineral oil, 20 mg, 0.50 mmol) and the resulting mixture was stirred at rt for 2 h. The reaction was quenched with water (5 mL) and was extracted with EtOAc (2×15 mL). Removal of solvent and chromatography of the crude residue on a silica gel column using a 10% mixture of EtOAc and hexane as solvents afforded 90 mg (86%) of 1-tert-butoxycarbonyl-1,2,3,4-tetrahydro-2,2,3-trimethyl-4-quinolinone as a colorless oil. The oil (90 mg, 0.32 mmol) was treated with NaBH4 (50 mg, 1.3 mmol) in methanol (5 mL) for 1 h and the reaction mixture was concentrated. Filtration from the inorganic material through a silica gel pad provided a colorless oil, which was then subjected to hydrogenation over 10% Pd/C (10 mg) in EtOAc (5 mL) under a hydrogen balloon for 15 h. Filtration from the catalyst through a Celite™ pad followed by removal of solvent gave 70 mg (82%) of 1-tert-butoxycarbonyl-1,2,3,4-tetrahydro-2,2,3-trimethylquinoline as a colorless oil. The crude oil (70 mg, 0.26 mmol) was treated with TFA (0.50 mL, 6.5 mmol) in CH2Cl2 for 30 min. and was quenched with 5% NaOH (6 mL). The mixture was extracted with EtOAc (2×15 mL) and was concentrated. Chromatography on silica gel using a 10% mixture of EtOAc and hexane afforded 1,2,3,4-tetrahydro-2,2,3-trimethylquinoline as a colorless oil (40 mg, 89%). Data for 1,2,3,4-tetrahydro-2,2,3-trimethylquinoline: 1H NMR (400 MHz, CDCl3) 7.00-6.91 (m, 2 H), 6.60 (t, J=7.3, 1 H), 6.45 (d, J=7.3, 1 H), 3.61 (br s, 1 H), 2.74 (dd, J=16.6, 5.3, 1 H), 2.47 (dd, J=16.6, 10.3, 1 H), 1.82 (m, 1 H), 1.20 (s, 3 H), 1.05 (s, 3 H), 0.97 (d, J=7.2, 3 H).

Workup

  1. customThe reaction was quenched with water (5 mL)
  2. extractionwas extracted with EtOAc (2×15 mL)
  3. customRemoval of solvent and chromatography of the crude residue on a silica gel column

Sources & evidence

ORD record
ord-a2e6193984414450a9b0bf4faff59092
Source dataset
uspto-grants-1997_12
Patent number
US05693646

Reaction notes

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