Sodium Hydroxide → HCID 72188143, compound

HRID 515203Notes

Reaction equation

HRID 515203 reaction equation
[CH:1]([C:4]1[CH:12]=[C:11]([N:13]2[CH2:18][CH2:17][O:16][CH2:15][CH2:14]2)[CH:10]=[C:9]([O:19][CH3:20])[C:5]=1[C:6]([NH2:8])=[O:7])([CH3:3])[CH3:2].[OH-].[Na+].[Cl:23][C:24]1[CH:31]=[CH:30][C:27]([CH2:28]Br)=[CH:26][CH:25]=1>O1CCCC1.C1C=CC=CC=1.S([O-])(O)(=O)=O.C([N+](CCCC)(CCCC)CCCC)CCC.O1CCCC1>[Cl:23][C:24]1[CH:31]=[CH:30][C:27]([CH2:28][NH:8][C:6](=[O:7])[C:5]2[C:9]([O:19][CH3:20])=[CH:10][C:11]([N:13]3[CH2:18][CH2:17][O:16][CH2:15][CH2:14]3)=[CH:12][C:4]=2[CH:1]([CH3:3])[CH3:2])=[CH:26][CH:25]=1

Participants

7

Reactant 3

HCID 14798Sodium HydroxideHCID 693291-(Bromomethyl)-4-chlorobenzeneHCID 86699767HCID 86699767, compound

Product 1

HCID 72188143HCID 72188143, compoundYield 40.9%

Reagents, catalysts & solvents 3

HCID 94433Tetrabutylammonium hydrogen sulfateCatalystHCID 8028TetrahydrofuranSolventHCID 22633675Benzene tetrahydrofuranSolvent

Conditions

Temperature
90 °C

Procedure

To a stirred solution of 2-isopropyl-6-methoxy-4-morpholin-4-yl-benzamide (0.31 g, 1.1 mmol) in tetrahydrofuran/benzene (1:2) (10 ml) is added tetrabutylammonium hydrogen sulfate (38.0 mg, 0.10 mmol) followed by the addition of 30% aqueous sodium hydroxide (10 ml) at room temperature. A solution of 4-chloro-benzyl bromide (0.23 g, 1.1 mmol) in tetrahydrofuran (4 ml) is slowly added to the solution and the resulting mixture is heated to 90° C. for 45 min. The mixture is cooled to room temperature and extracted with ethyl acetate (3×10 ml). The combined organic layers are washed with water (10 ml), brine (10 ml), dried over anhydrous sodium sulfate and concentrated in vacuo to get crude product, which is purified by flash column chromatography (silica gel, 10% acetone/hexane) to yield N-[(4-chlorophenyl)-methyl]-2-isopropyl-6-methoxy-4-morpholin-4-yl-benzamide (example 40) (0.115 g, 0.45 mmol, 28%). [M+H]+ 403.2.

Workup

  1. temperatureThe mixture is cooled to room temperature
  2. extractionextracted with ethyl acetate (3×10 ml)
  3. washThe combined organic layers are washed with water (10 ml), brine (10 ml)
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customto get crude product, which
  7. customis purified by flash column chromatography (silica gel, 10% acetone/hexane)

Sources & evidence

ORD record
ord-4c1ceadf482a43e3bcd3661887a65527
Source dataset
uspto-grants-2015_08
Patent number
US09108936B2

Reaction notes

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