Acetonitrile → 1-(2-chloro-5-(((R)-1-(3-chlorophenyl)ethylamino)methyl)phenoxy)propan-2-ol

HRID 1801605ノート

反応式

HRID 1801605 の反応式
CC#N.[Cl:4][C:5]1[CH:10]=[CH:9][C:8]([CH2:11][NH:12][C@@H:13]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([Cl:21])[CH:16]=2)[CH3:14])=[CH:7][C:6]=1[OH:22].[CH2:23]1[O:26][CH:24]1[CH3:25].C(=O)([O-])[O-].[Cs+].[Cs+]>CCOC(C)=O>[Cl:4][C:5]1[CH:10]=[CH:9][C:8]([CH2:11][NH:12][C@@H:13]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([Cl:21])[CH:16]=2)[CH3:14])=[CH:7][C:6]=1[O:22][CH2:23][CH:24]([OH:26])[CH3:25]

参加物

6

反応物 4

HCID 6342AcetonitrileHCID 6378Propylene OxideHCID 10796Cesium carbonateHCID 59803158(R)-2-chloro-5-((1-(3-chlorophenyl)ethylamino)methyl)phenol

生成物 1

HCID 249548221-(2-chloro-5-(((R)-1-(3-chlorophenyl)ethylamino)methyl)phenoxy)propan-2-ol収率 62%

試薬・触媒・溶媒 1

HCID 8857Ethyl Acetate溶媒

実験手順

A microwave compatible vial was charged with 2 mL of CH3CN, (R)-2-chloro-5-((1-(3-chlorophenyl)ethylamino)methyl)phenol 96 (115 mg, 388 μmol), propylene oxide (33 μL, 466 μmol), and cesium carbonate (139 mg, 427 μmol). The vial was sealed and was subjected to microwave irradiation at 140° C. for 30 min. The reaction was checked for completion by TLC. The reaction solution was diluted with EtOAc and it was washed with water (2×) and then 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 70% gradient of EtOAc in hexanes as the eluant. The desired fractions were combined and concentrated to give 1-(2-chloro-5-(((R)-1-(3-chlorophenyl)ethylamino)methyl)phenoxy)propan-2-ol 97 (85 mg, 62% yield), as a colorless oil and as a mixture of diastereomers. 1H NMR (400 MHz, d4-methanol) δ ppm 1.32 (d, J=6.46 Hz, 3H) 1.73 (d, J=6.85 Hz, 3H) 3.92-4.02 (m, 3H) 4.13-4.21 (m, 2H) 4.49 (q, J=6.78 Hz, 1H) 6.98 (dd, J=8.12, 1.66 Hz, 1H) 7.43-7.49 (m, 2H) 7.49-7.53 (m, 2H) 7.58 (s, 1H). Mass spectrum: calculated for C18H21Cl2NO2 354.3. found 355.4 (M++1).

後処理

  1. customThe vial was sealed
  2. customirradiation at 140° C. for 30 min
  3. washwas washed with water (2×)
  4. dry with materialThe organic layer was dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude material was purified by silica gel chromatography
  8. concentrationconcentrated

出典と根拠

ORDレコード
ord-4976134823764315b3a469e5328ffbc3
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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