Morpholine → HCID 59180433, compound

HRID 1925722Notes

Reaction equation

HRID 1925722 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([S:8]([NH:11][C:12]2[CH:16]=[CH:15][S:14][C:13]=2[C:17]([O:19][CH3:20])=[O:18])(=[O:10])=[O:9])=[CH:4][CH:3]=1.[NH:21]1[CH2:26][CH2:25][O:24][CH2:23][CH2:22]1.CC(C)([O-])C.[Na+].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=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.[Pd]>[O:24]1[CH2:25][CH2:26][N:21]([C:2]2[CH:7]=[CH:6][C:5]([S:8]([NH:11][C:12]3[CH:16]=[CH:15][S:14][C:13]=3[C:17]([O:19][CH3:20])=[O:18])(=[O:10])=[O:9])=[CH:4][CH:3]=2)[CH2:22][CH2:23]1

Participants

7

Reactant 4

HCID 8083MorpholineHCID 634876Binap, (A+-)-HCID 4643451HCID 4643451, compoundHCID 23676156Sodium t-butoxide

Product 1

HCID 59180433HCID 59180433, compoundYield 29.7%

Reagents, catalysts & solvents 2

HCID 6505921(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladiumCatalystHCID 1140TolueneSolvent2×

Conditions

Temperature
100 °C

Procedure

To a solution of 74 (1.02 g; 2.7 mmol) in anhydrous toluene (13.3 mL) were added morpholine (0.28 mL; 3.2 mmol), sodium tert-butoxide (0.52 g; 5.4 mmol), bis(dibenzylideneacetone)palladium(0) (79 mg; 0.1 mmol), and racemic-BINAP (104 mg; 0.2 mmol), sequentially. Additional toluene (13.3 mL) was added to aid in stirring. The reaction mixture was put under nitrogen atmosphere (flush×3) and then heated at 100° C. for 16 hours. After cooling to room temperature, the reaction mixture was extracted with dichloromethane (70 mL) and washed with aqueous hydrochloric acid (30 mL×2; 2N), water (30 mL), and aqueous saturated sodium chloride (30 mL). The dichloromethane extracts were dried over magnesium sulfate, filtered, and concentrated under reduced pressure to yield a yellow gel. The crude product was purified by silica gel chromatography (16% to 25% to 33% to 66% ethyl acetate in hexanes to 10% methanol in dichloromethane gradient) to yield the title compound as a pale yellow solid (307 mg).

Workup

  1. custom(flush×3)
  2. temperatureAfter cooling to room temperature
  3. extractionthe reaction mixture was extracted with dichloromethane (70 mL)
  4. washwashed with aqueous hydrochloric acid (30 mL×2; 2N), water (30 mL), and aqueous saturated sodium chloride (30 mL)
  5. dry with materialThe dichloromethane extracts were dried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customto yield a yellow gel
  9. customThe crude product was purified by silica gel chromatography (16% to 25% to 33% to 66% ethyl acetate in hexanes to 10% methanol in dichloromethane gradient)

Sources & evidence

ORD record
ord-789fc0bd92c44fa0a5449295e0bd1fff
Source dataset
uspto-grants-2012_05
Patent number
US08178699B2

Reaction notes

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