Lithium Chloride → tert-butyl 5-(pyridin-4-yl)-3,4-dihydroisoquinoline-2(1H)-carboxylate

HRID 1054135Notes

Reaction equation

Br[C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH2:4][CH2:5][N:6]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:7]2.C([Sn](CCCC)(CCCC)[C:24]1[CH:29]=[CH:28][N:27]=[CH:26][CH:25]=1)CCC.[Li+].[Cl-]>C1(C)C=CC=CC=1>[N:27]1[CH:28]=[CH:29][C:24]([C:2]2[CH:11]=[CH:10][CH:9]=[C:8]3[C:3]=2[CH2:4][CH2:5][N:6]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:7]3)=[CH:25][CH:26]=1

Participants

Conditions

Temperature: 110 °C

Procedure

(Tet. Lett, 1995, 36, 5247) To tert-butyl 5-bromo-3,4-dihydroisoquinoline- 2(1H)-carboxylate (0.989 g, 3.17 mmol), 4-(tributylstannyl)pyridine (1.75 g, 4.75 mmol), LiCl (1.343 g, 31.7 mmol) in toluene (15 mL) was added dichlorobis(triphenylphosphine) palladium (II) (0.222 g, 0.317 mmol) and the reaction was heated to 110° C. After 72 h, the reaction was partitioned with 10% aq KF (20 mL) and EtOAc (50 mL). The aqueous layer was extracted with EtOAc (2×50 mL). The combined organic layers were washed with brine (15 mL) and dried (MgSO4). Purification by silica gel chromatography afforded 0.63 g of Intermediate 17A as clear oil (64%). 1H NMR (400 MHz, CDCl3) δ 8.66 (2H, d, J=6.06 Hz), 7.23-7.33 (3H, m), 7.17-7.21 (1H, m), 7.13 (1H, d, J=7.58 Hz), 4.65 (2H, s), 3.55 (2H, br. s), 2.72 (2H, t, J=5.68 Hz), 1.50 (9H, s) ppm.

Workup

customthe reaction was partitioned with 10% aq KF (20 mL) and EtOAc (50 mL)
extractionThe aqueous layer was extracted with EtOAc (2×50 mL)
washThe combined organic layers were washed with brine (15 mL)
dry with materialdried (MgSO4)
customPurification by silica gel chromatography

Sources & evidence

ORD record: ord-ccd297e198b744aaba2afdc9b101d58d
Source dataset: uspto-grants-2016_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09394276B2

Reaction notes

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