Sodium Hydroxide → HCID 72187944, compound

HRID 515177Notes

Reaction equation

HRID 515177 reaction equation
C(O[C:4](=[O:21])[C:5]1[C:10]([CH3:11])=[CH:9][C:8]([N:12]2[CH2:17][CH2:16][O:15][CH2:14][CH2:13]2)=[CH:7][C:6]=1[CH:18]([F:20])[F:19])C.[Cl:22][C:23]1[CH:30]=[CH:29][C:26]([CH2:27][NH2:28])=[CH:25][CH:24]=1.C[Al](C)C.[OH-].[Na+]>C1(C)C=CC=CC=1>[Cl:22][C:23]1[CH:30]=[CH:29][C:26]([CH2:27][NH:28][C:4](=[O:21])[C:5]2[C:10]([CH3:11])=[CH:9][C:8]([N:12]3[CH2:13][CH2:14][O:15][CH2:16][CH2:17]3)=[CH:7][C:6]=2[CH:18]([F:19])[F:20])=[CH:25][CH:24]=1

Participants

6

Reactant 4

HCID 14798Sodium HydroxideHCID 660364-ChlorobenzylamineHCID 16682925TrimethylaluminumHCID 86699745HCID 86699745, compound

Product 1

HCID 72187944HCID 72187944, compoundYield 13%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of 2-(difluoro-methyl)-6-methyl-4-morpholin-4-yl-benzoic acid ethyl ester (0.30 g, 1.00 mmol), 4-chlorobenzylamine (1.42 g, 10.0 mmol) and trimethylaluminium (2M in toluene) (3.50 ml, 7.00 mmol) in toluene (10 ml) is heated at 110° C. for 18 h. After completion of the reaction (monitored by TLC), a 2M aqueous solution of sodium hydroxide is carefully added and the mixture is extracted with ethyl acetate (2×15 ml). The combined organic layers are washed with 2M aqueous solution of sodium hydroxide (10 ml), brine (10 ml) and dried over sodium sulfate. The solvent is evaporated to get the crude product, which is purified by column chromatography (silica gel, 30% ethyl acetate/cyclohexane) to afford N-[(4-chlorophenyl)-methyl]-2-(difluoro-methyl)-6-methyl-4-morpholin-4-yl-benzamide (example 20) (0.05 g, 0.13 mmol, 13%). [M+H]+ 395.1.

Workup

  1. customAfter completion of the reaction (monitored by TLC)
  2. extractionthe mixture is extracted with ethyl acetate (2×15 ml)
  3. washThe combined organic layers are washed with 2M aqueous solution of sodium hydroxide (10 ml), brine (10 ml)
  4. dry with materialdried over sodium sulfate
  5. customThe solvent is evaporated
  6. customto get the crude product, which
  7. customis purified by column chromatography (silica gel, 30% ethyl acetate/cyclohexane)

Sources & evidence

ORD record
ord-1e573278a6a64abcba280c3fe7dcb8d1
Source dataset
uspto-grants-2015_08
Patent number
US09108936B2

Reaction notes

Loading…