Ammonium Chloride → 1-[2-[(4S)-4-(tert-butyldimethyl-silyloxy)-1,2,3,4-tetrahydroquinolin-1-yl]-4-pyridyl]-2,3-bis(methoxycarbonyl)-6,7-dimethoxynaphthalene

HRID 407119Notes

Reaction equation

HRID 407119 reaction equation
Br[C:2]1[CH:7]=[C:6]([C:8]2[C:17]3[C:12](=[CH:13][C:14]([O:20][CH3:21])=[C:15]([O:18][CH3:19])[CH:16]=3)[CH:11]=[C:10]([C:22]([O:24][CH3:25])=[O:23])[C:9]=2[C:26]([O:28][CH3:29])=[O:27])[CH:5]=[CH:4][N:3]=1.F[B-](F)(F)F.C([PH+](C(C)(C)C)C(C)(C)C)(C)(C)C.[Si:48]([O:55][C@@H:56]1[C:65]2[C:60](=[CH:61][CH:62]=[CH:63][CH:64]=2)[NH:59][CH2:58][CH2:57]1)([C:51]([CH3:54])([CH3:53])[CH3:52])([CH3:50])[CH3:49].CC(C)([O-])C.[Na+].[Cl-].[NH4+]>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(OCC)(=O)C.O>[Si:48]([O:55][C@@H:56]1[C:65]2[C:60](=[CH:61][CH:62]=[CH:63][CH:64]=2)[N:59]([C:2]2[CH:7]=[C:6]([C:8]3[C:17]4[C:12](=[CH:13][C:14]([O:20][CH3:21])=[C:15]([O:18][CH3:19])[CH:16]=4)[CH:11]=[C:10]([C:22]([O:24][CH3:25])=[O:23])[C:9]=3[C:26]([O:28][CH3:29])=[O:27])[CH:5]=[CH:4][N:3]=2)[CH2:58][CH2:57]1)([C:51]([CH3:54])([CH3:53])[CH3:52])([CH3:50])[CH3:49]

Participants

10

Reactant 5

HCID 25517Ammonium ChlorideHCID 2734635Tri-tert-butylphosphine tetrafluoroborateHCID 220073291-(2-Bromo-4-pyridyl)-2,3-bis(methoxycarbonyl)-6,7-dimethoxynaphthaleneHCID 23676156Sodium t-butoxideHCID 66866618(4S)-4-(tert-butyldimethylsilyloxy)-1,2,3,4-tetrahydroquinoline

Product 1

HCID 668676711-[2-[(4S)-4-(tert-butyldimethyl-silyloxy)-1,2,3,4-tetrahydroquinolin-1-yl]-4-pyridyl]-2,3-bis(methoxycarbonyl)-6,7-dimethoxynaphthaleneYield 80%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

A solution of 20.00 g of 1-(2-bromo-4-pyridyl)-2,3-bis(methoxycarbonyl)-6,7-dimethoxynaphthalene in 200 mL of toluene was sonicated under reduced pressure, and then to the solution were added 975 mg of palladium acetate, 1009 mg of tri-tert-butylphosphonium tetrafluoroborate, 13.72 g of (4S)-4-(tert-butyldimethylsilyloxy)-1,2,3,4-tetrahydroquinoline and 6.26 g of sodium tert-butoxide at room temperature. After nitrogen substitution, the mixture was stirred at 100° C. for 4 hours. After radiation, to the reaction solution were added 100 mL of saturated aqueous ammonium chloride solution, 100 mL of water and 100 mL of ethyl acetate, and the mixture was filtered through Celite®. Celite® was washed with 100 mL of ethyl acetate, and then the organic layer was separated. The organic layer was washed with 100 g of 20% saline, dried over magnesium sulfate, and then concentrated. The resulting residue was purified by column chromatography on silica gel (n-hexan/ethyl acetate=5/1 to 4/1) to give 22.31 g of 1-[2-[(4S)-4-(tert-butyldimethylsilyloxy)-1,2,3,4-tetrahydroquinolin-1-yl]-4-pyridyl]-2,3-bis(methoxycarbonyl)-6,7-dimethoxynaphthalene (yield: 80%).

Workup

  1. filtrationthe mixture was filtered through Celite®
  2. washCelite® was washed with 100 mL of ethyl acetate
  3. customthe organic layer was separated
  4. washThe organic layer was washed with 100 g of 20% saline
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated
  7. customThe resulting residue was purified by column chromatography on silica gel (n-hexan/ethyl acetate=5/1 to 4/1)

Sources & evidence

ORD record
ord-9eeaa7a1c1fc4f50bff5b555ad949f3c
Source dataset
uspto-grants-2014_06
Patent number
US08754221B2

Reaction notes

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