Sodium Hydroxide → HCID 72187840, compound

HRID 515149Notes

Reaction equation

HRID 515149 reaction equation
[CH2:1]([S:3][C:4]1[CH:12]=[C:11]([N:13]2[CH2:18][CH2:17][O:16][CH2:15][C@H:14]2[CH3:19])[CH:10]=[C:9]([CH3:20])[C:5]=1[C:6]([NH2:8])=[O:7])[CH3:2].[OH-].[Na+].[Cl:23][C:24]1[CH:31]=[CH:30][C:27]([CH2:28]Br)=[CH:26][CH:25]=1>C1C=CC=CC=1.O1CCCC1.S([O-])(O)(=O)=O.C([N+](CCCC)(CCCC)CCCC)CCC>[Cl:23][C:24]1[CH:31]=[CH:30][C:27]([CH2:28][NH:8][C:6](=[O:7])[C:5]2[C:9]([CH3:20])=[CH:10][C:11]([N:13]3[CH2:18][CH2:17][O:16][CH2:15][C@H:14]3[CH3:19])=[CH:12][C:4]=2[S:3][CH2:1][CH3:2])=[CH:26][CH:25]=1

Participants

6

Reactant 3

HCID 14798Sodium HydroxideHCID 693291-(Bromomethyl)-4-chlorobenzeneHCID 866997262-ethylsulfanyl-6-methyl-4-[(3R)-3-methyl-morpholin-4-yl]-benzamide

Product 1

HCID 72187840HCID 72187840, compoundYield 32.4%

Reagents, catalysts & solvents 2

HCID 94433Tetrabutylammonium hydrogen sulfateCatalystHCID 22633675Benzene tetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of 2-ethylsulfanyl-6-methyl-4-[(3R)-3-methyl-morpholin-4-yl]-benzamide (0.05 g, 0.17 mmol) in benzene-tetrahydrofuran (1:1) (2 ml) are added tetrabutylammonium hydrogensulfate (0.006 g, 0.017 mmol) and 50% sodium hydroxide solution (1.5 ml) at RT. 4-Chlorobenzyl bromide (0.038 g, 0.19 mmol) is added and the reaction mixture is slowly heated to 70° C. The reaction mixture is stirred at 70° C. for additional 45 min. After completion of the reaction (monitored by TLC), the organic layer is separated and the aqueous layer is extracted with ethyl acetate (2×20 ml). The organic layer is washed with water (20 ml), brine (20 ml), dried over anhydrous sodium sulfate and evaporated to get the crude product, which is purified by column chromatography (silica gel, 8% acetone/hexane) to yield N-[(4-chlorophenyl)-methyl]-2-ethylsulfanyl-6-methyl-4-[(3R)-3-methyl-morpholin-4-yl]-benzamide (example 4) (0.023 g, 0.055 mmol, 32%). [M+H]+ 419.2.

Workup

  1. customAfter completion of the reaction (monitored by TLC)
  2. customthe organic layer is separated
  3. extractionthe aqueous layer is extracted with ethyl acetate (2×20 ml)
  4. washThe organic layer is washed with water (20 ml), brine (20 ml)
  5. dry with materialdried over anhydrous sodium sulfate
  6. customevaporated
  7. customto get the crude product, which
  8. customis purified by column chromatography (silica gel, 8% acetone/hexane)

Sources & evidence

ORD record
ord-7d9eac8bc356473ea788768dc132f382
Source dataset
uspto-grants-2015_08
Patent number
US09108936B2

Reaction notes

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