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

HRID 1801605Notes

Reaction equation

HRID 1801605 reaction equation
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]

Participants

6

Reactant 4

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

Product 1

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

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-4976134823764315b3a469e5328ffbc3
Source dataset
uspto-grants-2013_01
Patent number
US08349831B2

Reaction notes

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