Sodium Carbonate → HCID 24955180, compound

HRID 1801614Notes

Reaction equation

HRID 1801614 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:15]=[C:16]([O:20][CH3:21])[C:17]=1[O:18][CH3:19])[CH2:5][NH:6][C@@H:7]([C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)[CH3:8].[CH3:22][O:23][C:24]1[CH:29]=[CH:28][C:27](B(O)O)=[CH:26][CH:25]=1.C([O-])([O-])=O.[Na+].[Na+].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C([O-])(O)=O.[Na+]>C1(C)C=CC=CC=1.CCOC(C)=O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CCO>[CH3:22][O:23][C:24]1[CH:29]=[CH:28][C:27]([C:2]2[CH:3]=[C:4]([CH:15]=[C:16]([O:20][CH3:21])[C:17]=2[O:18][CH3:19])[CH2:5][NH:6][C@@H:7]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH3:8])=[CH:26][CH:25]=1

Participants

10

Reactant 5

HCID 10340Sodium CarbonateHCID 11776TriphenylphosphineHCID 201262(4-Methoxyphenyl)boronic acidHCID 516892Sodium BicarbonateHCID 40761829HCID 40761829, compound

Product 1

HCID 24955180HCID 24955180, compoundYield 42.1%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

To a mixture of (R)—N-(3-bromo-4,5-dimethoxybenzyl)-1-phenylethanamine 112 (1.1 g, 3.15 mmol), 4-methoxyphenylboronic acid (0.48 g, 3.15 mmol, Aldrich) and 2M Na2CO3 (5.0 mL) in 10 mL of toluene was added PPh3 (83 mg, 0.315 mmol) and Pd(PPh3)4 (0.364 g, 0.315 mmol) at room temp. under N2. The reaction mixture was then heated up to 80° C. under N2 atmosphere overnight. EtOH (4 mL) was added and the reaction was continued at 80° C. for 4 hours. The reaction was cooled to room temp. and diluted with 50 mL of EtOAc and 20 mL of sat'd. NaHCO3 aq. solution. The organic phase was separated, washed with 20 mL of brine, dried over Na2SO4 and concentrated in vacuo. The residue was purified by a silica gel column chromatography (10% EtOAc/hexane to 50% EtOAc/hexane) to afford light yellow oil as desired product (R)—N-(3-(4-Methoxyphenyl)-4,5-dimethoxybenzyl)-1-phenylethanamine 113 (0.5 g, 42%). MS (ESI, pos. ion) m/z: 378.0 (M+1). 1H NMR (400 MHz, CDCl3) δ ppm 10.0-10.2 (br, 2H), 6.8-7.5 (m, 9H), 6.8 (s, 1H); 6.7 (s, 1H), 3.9 (m, 1H); 3.7-3.8 (m, 1H), 3.8 (s, 3H); 3.7 (s, 3H); 3.4 (m, 1H), 3.2 (s, 3H), 1.7 (d, J=7.0 Hz, 3H).

Workup

  1. temperatureThe reaction was cooled to room temp.
  2. customThe organic phase was separated
  3. washwashed with 20 mL of brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by a silica gel column chromatography (10% EtOAc/hexane to 50% EtOAc/hexane)

Sources & evidence

ORD record
ord-d0d187dd047b47f18d64f4e0949485b0
Source dataset
uspto-grants-2013_01
Patent number
US08349831B2

Reaction notes

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