Dimethyl Sulfoxide → (R)-Tert-butyl 3-formyl-3,4-dihydroisoquinoline-2(1H)-carboxylate

HRID 601700Notes

Reaction equation

C(Cl)(=O)C(Cl)=O.CS(C)=O.[C:11]([O:15][C:16]([N:18]1[C@@H:27]([C:28](O)=[O:29])[CH2:26][C:25]2[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=2)[CH2:19]1)=[O:17])([CH3:14])([CH3:13])[CH3:12].C(N(CC)CC)C.C(=O)([O-])[O-].[Na+].[Na+]>ClCCl>[CH:28]([C@H:27]1[CH2:26][C:25]2[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=2)[CH2:19][N:18]1[C:16]([O:15][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:17])=[O:29]

Participants

Conditions

Temperature: -78 °C

Procedure

To a solution of oxalyl dichloride (1.14 g, 9 mmol) in dichloromethane (30 mL) was added dimethyl sulfoxide (1.4 g, 18 mmol) at −78° C. After stirring at −78° C. for 20 min, to the mixture was added a solution of (R)-tert-butyl3-(hydroxymethyl)-3,4-dihydroisoquinoline-2(1H)-carboxylate (Step A (2), 1.32 g, 5 mmol) in dichloromethane (30 mL) and stirred at −78° C. for 30 to 45 min. Then triethylamine (36 mmol) was added and the reaction mixture was warmed up to rt over 2 h. Saturated sodium carbonate solution was added and extracted with dichloromethane. The solvent was removed and the crude mixture was purified by silica gel Flash chromatography to give the title compound: 1.2 g (90% yield). 1H NMR (CDCl3, 500 MHz) δ 1.48 (9H, d, J=35 Hz), 3.06-3.62 (2H, m), 4.45-4.81 (3H, m), 7.09-7.19 (4H, m), 9.48 (1H, d, J=25 Hz).

Workup

stirringstirred at −78° C. for 30 to 45 min
temperaturethe reaction mixture was warmed up to rt over 2 h
extractionextracted with dichloromethane
customThe solvent was removed
customthe crude mixture was purified by silica gel Flash chromatography

Sources & evidence

ORD record: ord-d22360bc9ac241ad8eb87ebda1709aea
Source dataset: uspto-grants-2011_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07902218B2

Reaction notes

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