Triphenylphosphine → (1R)-N-(4-chloro-3-(1-(methylsulfonyl)pyrrolidin-3-yloxy)benzyl)-1-(3-chlorophenyl)ethanamine

HRID 1801607ノート

反応式

HRID 1801607 の反応式
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][NH:9][C@@H:10]([C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([Cl:18])[CH:13]=2)[CH3:11])=[CH:4][C:3]=1[OH:19].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O.[CH3:53][S:54]([N:57]1[CH2:61][CH2:60][CH:59](O)[CH2:58]1)(=[O:56])=[O:55]>C1COCC1>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][NH:9][C@@H:10]([C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([Cl:18])[CH:13]=2)[CH3:11])=[CH:4][C:3]=1[O:19][CH:59]1[CH2:60][CH2:61][N:57]([S:54]([CH3:53])(=[O:56])=[O:55])[CH2:58]1

参加物

6

反応物 4

HCID 11776TriphenylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 207458431-Methanesulfonylpyrrolidin-3-olHCID 59803158(R)-2-chloro-5-((1-(3-chlorophenyl)ethylamino)methyl)phenol

生成物 1

HCID 24954824(1R)-N-(4-chloro-3-(1-(methylsulfonyl)pyrrolidin-3-yloxy)benzyl)-1-(3-chlorophenyl)ethanamine収率 37%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
0 °C

実験手順

To a solution of (R)-2-chloro-5-((1-(3-chlorophenyl)ethylamino)methyl)phenol 96 (150 mg, 506 μmol) in 5 mL of THF under N2 was added triphenylphosphine (146 mg, 557 μmol). The solution was chilled to 0° C. in an ice bath and then diisopropyl azodicarboxylate (108 μL, 557 μmol) was added dropwise to the reaction. After stirring for 15 min 0° C., a solution of 1-(methylsulfonyl)pyrrolidin-3-ol (84 mg, 506 μmol) in THF was added to the reaction. The reaction was allowed to warm to room temperature and it was stirred for 10 h. The reaction was concentrated and diluted with EtOAc. The organic solution was extracted with saturated NaHCO3, water, and brine. The organic layer was dried over MgSO4, filtered, and concentrated in vacuo. The crude material was purified by silica gel chromatography using a 10% to 80% gradient of EtOAc in hexanes as the eluant. The desired fractions were combined and concentrated to give (1R)—N-(4-chloro-3-(1-(methylsulfonyl)pyrrolidin-3-yloxy)benzyl)-1-(3-chlorophenyl)ethanamine 99 (83 mg, 37% yield) as a colorless oil and as a mixture of diastereomers. 1H NMR (400 MHz, d4-methanol) δ ppm 1.26 (d, 1H) 1.73 (d, J=6.85 Hz, 3H) 2.25-2.32 (m, 2H) 2.91 (s, 3H) 3.51-3.60 (m, 2H) 3.62-3.66 (m, 2H) 4.00 (d, 1H) 4.20 (d, 1H) 4.50 (m, 1H) 5.08-5.13 (m, 1H) 6.99-7.07 (m, 1H) 7.14-7.18 (m, 1H) 7.43-7.52 (m, 4H) 7.57 (m, 1H). Mass spectrum: calculated for C20H24Cl2N2O3S 443.4. found 444.4 (M++1).

後処理

  1. temperatureto warm to room temperature
  2. stirringit was stirred for 10 h
  3. concentrationThe reaction was concentrated
  4. additiondiluted with EtOAc
  5. extractionThe organic solution was extracted with saturated NaHCO3, water, and brine
  6. dry with materialThe organic layer was dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe crude material was purified by silica gel chromatography
  10. concentrationconcentrated

出典と根拠

ORDレコード
ord-d4e09d505fa64abcba5eb4c42c81026e
出典データセット
uspto-grants-2013_01
特許番号
US08349831B2

反応ノート

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