Morpholine → HCID 72188144, compound

HRID 515208Notes

Reaction equation

HRID 515208 reaction equation
Br[C:2]1[CH:18]=[C:17]([CH2:19][CH3:20])[C:5]([C:6]([NH:8][CH2:9][C:10]2[CH:15]=[CH:14][C:13]([Cl:16])=[CH:12][CH:11]=2)=[O:7])=[C:4]([CH2:21][CH3:22])[CH:3]=1.[NH:23]1[CH2:28][CH2:27][O:26][CH2:25][CH2:24]1.C(=O)([O-])[O-].[Cs+].[Cs+].C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Cl:16][C:13]1[CH:14]=[CH:15][C:10]([CH2:9][NH:8][C:6](=[O:7])[C:5]2[C:17]([CH2:19][CH3:20])=[CH:18][C:2]([N:23]3[CH2:28][CH2:27][O:26][CH2:25][CH2:24]3)=[CH:3][C:4]=2[CH2:21][CH3:22])=[CH:11][CH:12]=1

Participants

7

Reactant 4

HCID 8083MorpholineHCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 86699769HCID 86699769, compound

Product 1

HCID 72188144HCID 72188144, compoundYield 52.2%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
120 °C

Procedure

To a solution of 4-bromo-N-[(4-chlorophenyl)-methyl]-2,6-diethyl-benzamide (0.34 g, 0.90 mmol) in toluene (3 ml), morpholine (0.11 g, 1.29 mmol), caesium carbonate (0.40 g, 1.22 mmol) and 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (0.06 g, 0.09 mmol) are added. After degassing with argon for 30 min tris(dibenzylideneacetone)-dipalladium(0) (0.04 g, 0.04 mmol) are added and the mixture is heated at 120° C. for 16 h. After completion of the reaction (monitored by TLC) the mixture is filtered through a pad of celite and diluted with ethyl acetate (30 ml), the organic layer is washed with water and dried over sodium sulfate and concentrated in vacuo. The resulting crude product is purified by preparative HPLC to obtain the N-[(4-chlorophenyl)-methyl]-2,6-diethyl-4-morpholin-4-yl-benzamide (example 41) (0.18 g, 0.47 mmol, 26%). [M+H]+ 387.2.

Workup

  1. additionare added
  2. customAfter completion of the reaction (monitored by TLC) the mixture
  3. filtrationis filtered through a pad of celite
  4. additiondiluted with ethyl acetate (30 ml)
  5. washthe organic layer is washed with water
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated in vacuo
  8. customThe resulting crude product is purified by preparative HPLC

Sources & evidence

ORD record
ord-70ca683082fd43a79b1ae242ab56cb69
Source dataset
uspto-grants-2015_08
Patent number
US09108936B2

Reaction notes

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