Morpholine → HCID 86699740, compound

HRID 515171Notes

Reaction equation

HRID 515171 reaction equation
Br[C:2]1[CH:18]=[C:17]([CH3:19])[C:5]([C:6]([NH:8][CH2:9][C:10]2[CH:15]=[CH:14][C:13]([F:16])=[CH:12][CH:11]=2)=[O:7])=[C:4]([O:20][CH3:21])[CH:3]=1.[NH:22]1[CH2:27][CH2:26][O:25][CH2:24][CH2:23]1.CC(C)([O-])C.[Na+].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>CN1CCCC1=O.O.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]>[F:16][C:13]1[CH:14]=[CH:15][C:10]([CH2:9][NH:8][C:6](=[O:7])[C:5]2[C:17]([CH3:19])=[CH:18][C:2]([N:22]3[CH2:27][CH2:26][O:25][CH2:24][CH2:23]3)=[CH:3][C:4]=2[O:20][CH3:21])=[CH:11][CH:12]=1

Participants

8

Reactant 4

HCID 8083MorpholineHCID 634876Binap, (A+-)-HCID 23676156Sodium t-butoxideHCID 86699739HCID 86699739, compound

Product 1

HCID 86699740HCID 86699740, compoundYield 91%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
40 °C

Procedure

To a stirred solution of 4-bromo-N-[(4-fluorophenyl)-methyl]-2-methoxy-6-methyl-benzamide (2.7 g, 7.67 mmol) in N-methyl-2-pyrrolidone (10 ml) is added morpholine (0.93 g, 10.7 mmol) at RT. The reaction mixture is degassed and flushed with argon for 30 min followed by addition of sodium tert-butoxide (0.95 g, 9.9 mmol). The reaction mixture is heated to 40° C. At this temperature are added tris(dibenzylideneacetone)dipalladium(0) (0.31 g, 0.34 mmol) and 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (0.47 g, 0.76 mmol) and stirred at 100° C. for 12 h. After completion of the reaction (monitored by TLC), the mixture is diluted with water (50 ml) and extracted with ethyl acetate (3×75 ml). The organic layer is washed with water (50 ml), brine (50 ml), dried over anhydrous sodium sulfate and evaporated to get the crude product, which is purified by column chromatography (silica gel, 40% acetone/hexane) to yield N-[(4-fluorophenyl)-methyl]-2-methoxy-6-methyl-4-morpholin-4-yl-benzamide (2.50 g, 6.90 mmol, 91%).

Workup

  1. customThe reaction mixture is degassed
  2. customflushed with argon for 30 min
  3. customAfter completion of the reaction (monitored by TLC)
  4. extractionextracted with ethyl acetate (3×75 ml)
  5. washThe organic layer is washed with water (50 ml), brine (50 ml)
  6. dry with materialdried over anhydrous sodium sulfate
  7. customevaporated
  8. customto get the crude product, which
  9. customis purified by column chromatography (silica gel, 40% acetone/hexane)

Sources & evidence

ORD record
ord-02e77df3d0654ef687ece2e465bc5c79
Source dataset
uspto-grants-2015_08
Patent number
US09108936B2

Reaction notes

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