Sodium Carbonate → HCID 67244310, compound

HRID 2422893Notes

Reaction equation

HRID 2422893 reaction equation
C(OC(=O)[NH:7][C@@H:8]([C:10]1[CH:15]=[CH:14][C:13](Br)=[CH:12][CH:11]=1)[CH3:9])(C)(C)C.[Cl:18][C:19]1[CH:20]=[CH:21][C:22]([O:28][CH3:29])(B(O)O)[NH:23][CH:24]=1.C(=O)([O-])[O-].[Na+].[Na+]>C1(C)C=CC=CC=1.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[Cl:18][C:19]1[CH:20]=[C:21]([C:13]2[CH:12]=[CH:11][C:10]([C@H:8]([NH2:7])[CH3:9])=[CH:15][CH:14]=2)[C:22]([O:28][CH3:29])=[N:23][CH:24]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 52987808(R)-tert-Butyl (1-(4-bromophenyl)ethyl)carbamateHCID 86613383HCID 86613383, compound

Product 1

HCID 67244310HCID 67244310, compoundYield 77.8%

Reagents, catalysts & solvents 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
0 °C

Procedure

To a suspension of (R)-1-(4-bromophenyl)ethylamine (23.89 g, 0.101 mol) in tetrahydrofuran (200 ml) was added triethylamine (21 ml), 4-dimethylaminopyridine (1.5 g) and di-tert-butyldicarbonate (26.5 g, 0.121 mol). The solution was stirred overnight then diluted with diethyl ether and washed with 2M aqueous hydrogen chloride solution, 10% aqueous sodium carbonate solution and brine. The organic phase was dried over anhydrous sodium sulfate and the solution concentrated to low volume. Heptane was added and the resulting white solid filtered off and dried to give (R)-[1-(4-bromophenyl)-ethyl]-carbamic acid tert-butyl ester (17 g). To a solution of (R)-[1-(4-bromophenyl)-ethyl]-carbamic acid tert-butyl ester (2 g, 6.7 mmol) in toluene (40 ml) was added 5-chloro-2-methoxypyridine boronic acid (2.5 g, 13.3 mmol), 2M aqueous sodium carbonate solution (6.8 ml) and tetrakis(triphenylphosphine) palladium (0) (0.4 g). The solution was heated under reflux for 48 h then washed with water, brine and dried over anhydrous sodium sulfate. The solvent was evaporated and the residue dissolved in dichloromethane (50 ml) and the solution cooled to 0° C. Trifluoroacetic acid (20 ml) was added and the solution stirred for 3 h then evaporated to a gum which was chromatographed on a SCX column eluting with methanol then ammonia/methanol. The solvent was removed and the residue flash chromatographed on silica eluting with 9:1 dichloromethane/methanol then 9:1 dichloromethane/methanol-ammonia. The solvent was evaporated to give (R)-1-[4-(5-chloro-2-methoxy-pyridin-3-yl)-phenyl]-ethylamine (1.37 g) as a gum.

Workup

  1. temperatureThe solution was heated
  2. temperatureunder reflux for 48 h
  3. washthen washed with water, brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. customThe solvent was evaporated
  6. dissolutionthe residue dissolved in dichloromethane (50 ml)
  7. additionTrifluoroacetic acid (20 ml) was added
  8. customthen evaporated to a gum which
  9. customwas chromatographed on a SCX column
  10. washeluting with methanol
  11. customThe solvent was removed
  12. customthe residue flash chromatographed on silica eluting with 9:1 dichloromethane/methanol
  13. customThe solvent was evaporated

Sources & evidence

ORD record
ord-d42d28c44caf42538308623f63a1f48b
Source dataset
uspto-grants-2011_06
Patent number
US07960365B2

Reaction notes

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