Potassium Carbonate → HCID 59418747, compound

HRID 2178256Notes

Reaction equation

HRID 2178256 reaction equation
CC1(C)C(C)(C)OB([C:9]2[CH:18]=[C:17]3[C:12]([CH2:13][CH2:14][CH2:15][NH:16]3)=[CH:11][CH:10]=2)O1.[CH2:20]([O:27][C:28]1[C:29]([C:35]([O:37][CH3:38])=[O:36])=[N:30][C:31](Br)=[CH:32][CH:33]=1)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.C([O-])([O-])=O.[K+].[K+].O1CCOCC1>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O>[CH2:20]([O:27][C:28]1[C:29]([C:35]([O:37][CH3:38])=[O:36])=[N:30][C:31]([C:9]2[CH:18]=[C:17]3[C:12]([CH2:13][CH2:14][CH2:15][NH:16]3)=[CH:11][CH:10]=2)=[CH:32][CH:33]=1)[C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 312751,4-DioxaneHCID 59418684Methyl 3-(benzyloxy)-6-bromopicolinateHCID 594187157-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,4-tetrahydroquinoline

Product 1

HCID 59418747HCID 59418747, compound

Reagents, catalysts & solvents 3

HCID 74236Tetrabutylammonium BromideCatalystHCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
90 °C

Procedure

To 7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,4-tetrahydroquinoline (27B) (1.16 g, 4.48 mmol), methyl 3-(benzyloxy)-6-bromopicolinate (29A) (1.44 g, 4.48 mmol), K2CO3 (1.546 g, 11.2 mmol), tetrabutylammonium bromide (0.144 g, 0.45 mmol), and dichlorobis(triphenylphosphine)palladium(II) (126 mg, 0.18 mmol) was added 1,4-dioxane (30 mL) and water (15 mL). The reaction mixture was heated to 90° C. for 1.5 hours, cooled to rt, concentrated, diluted with EtOAc, washed sequentially with water, brine, dried over MgSO4, filtered, and concentrated under reduced pressure. The crude material was precipitated from EtOAc/PE to provide the product methyl 3-(benzyloxy)-6-(1,2,3,4-tetrahydroquinolin-7-yl)picolinate (29B). Additional material was isolated from the filtrate by column chromatography on silica gel eluting with a gradient of PE:EtOAc 73:27-63:37, to provide the desired product (29B): 1H NMR (300 MHz, CDCl3) δ7.67 (1H, d), 7.48-7.44 (2H, m), 7.43-7.31 (4H, m), 7.21 (1H, d), 7.16 (1H, dd), 7.01 (1H, d) 5.21 (2H, s), 3.98 (3H, s), 3.34 (2H, m), 2.79 (2H, t), 1.96 (2H, m).

Workup

  1. temperaturecooled to rt
  2. concentrationconcentrated
  3. additiondiluted with EtOAc
  4. washwashed sequentially with water, brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe crude material was precipitated from EtOAc/PE

Sources & evidence

ORD record
ord-f7ba5189f03a42589e3125f513f14819
Source dataset
uspto-grants-2015_06
Patent number
US09067928B2

Reaction notes

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