Chlorosuccinimide → Methyl 8-chloro-1-oxo-7-(propan-2-yloxy)-1,2,3,4-tetrahydroisoquinoline-5-carboxylate

HRID 577440Notes

Reaction equation

[O:1]=[C:2]1[C:11]2[CH:10]=[C:9]([O:12][CH:13]([CH3:15])[CH3:14])[CH:8]=[C:7]([C:16]([O:18][CH3:19])=[O:17])[C:6]=2[CH2:5][CH2:4][NH:3]1.C1C(=O)N([Cl:27])C(=O)C1>CC(O)=O>[Cl:27][C:10]1[C:11]2[C:2](=[O:1])[NH:3][CH2:4][CH2:5][C:6]=2[C:7]([C:16]([O:18][CH3:19])=[O:17])=[CH:8][C:9]=1[O:12][CH:13]([CH3:15])[CH3:14]

Participants

Conditions

Temperature: 100 °C

Procedure

To a solution of methyl 1-oxo-7-(propan-2-yloxy)-1,2,3,4-tetrahydroisoquinoline-5-carboxylate (Cpd E, 400 mg, 1.52 mmol) in AcOH (5 mL) was added NCS (416 mg, 3.04 mmol). The reaction mixture was stirred at 100° C. overnight. The reaction mixture was concentrated under vacuum and the residue was diluted with H2O and NaHCO3 (sat., aq.). The aqueous layer was extracted with EtOAc and the organic layer purified by column chromatography (50% EtOAc/heptanes) to give the title compound (Cpd F, 180 mg, 40%) as a white solid. 1H NMR (400 MHz, chloroform-d) δ 1.40 (s, 3H) 1.42 (s, 3H) 3.27-3.36 (m, 2H) 3.37-3.47 (m, 2H) 3.88-3.95 (m, 3H) 4.62 (dt, J=12.07, 6.13 Hz, 1H) 6.06 (br. s., 1H) 7.61 (s, 1H); MS 298.0 [M+H].

Workup

concentrationThe reaction mixture was concentrated under vacuum
additionthe residue was diluted with H2O and NaHCO3 (sat., aq.)
extractionThe aqueous layer was extracted with EtOAc
customthe organic layer purified by column chromatography (50% EtOAc/heptanes)

Sources & evidence

ORD record: ord-7c85c1f4d45d460c90f0da1e42c4f42f
Source dataset: uspto-grants-2015_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09040515B2

Reaction notes

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