Sodium Carbonate → HCID 67244310、化合物

HRID 2422893ノート

反応式

HRID 2422893 の反応式
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

参加物

6

反応物 3

HCID 10340Sodium CarbonateHCID 52987808(R)-tert-Butyl (1-(4-bromophenyl)ethyl)carbamateHCID 86613383HCID 86613383、化合物

生成物 1

HCID 67244310HCID 67244310、化合物収率 77.8%

試薬・触媒・溶媒 2

HCID 11979704Tetrakis(triphenylphosphine)palladium触媒HCID 1140Toluene溶媒

反応条件

温度
0 °C

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-d42d28c44caf42538308623f63a1f48b
出典データセット
uspto-grants-2011_06
特許番号
US07960365B2

反応ノート

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