Cesium carbonate → Methyl 3-[[5-(1,4-dioxa-8-azaspiro[4.5]decan-8-yl)-2-methyl-benzoyl]amino]-2,4-dimethyl-benzoate

HRID 239952Notes

Reaction equation

HRID 239952 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([CH3:23])=[C:6]([CH:22]=1)[C:7]([NH:9][C:10]1[C:11]([CH3:21])=[C:12]([CH:17]=[CH:18][C:19]=1[CH3:20])[C:13]([O:15][CH3:16])=[O:14])=[O:8].[O:24]1[C:28]2([CH2:33][CH2:32][NH:31][CH2:30][CH2:29]2)[O:27][CH2:26][CH2:25]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>O1CCOCC1.O.CC([O-])=O.CC([O-])=O.[Pd+2]>[O:24]1[C:28]2([CH2:33][CH2:32][N:31]([C:2]3[CH:3]=[CH:4][C:5]([CH3:23])=[C:6]([CH:22]=3)[C:7]([NH:9][C:10]3[C:11]([CH3:21])=[C:12]([CH:17]=[CH:18][C:19]=3[CH3:20])[C:13]([O:15][CH3:16])=[O:14])=[O:8])[CH2:30][CH2:29]2)[O:27][CH2:26][CH2:25]1

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 674351,4-Dioxa-8-azaspiro(4.5)decaneHCID 634876Binap, (A+-)-2×HCID 86707319Methyl 3-[(5-bromo-2-methyl-benzoyl)amino]-2,4-dimethyl-benzoate

Product 1

HCID 86707339Methyl 3-[[5-(1,4-dioxa-8-azaspiro[4.5]decan-8-yl)-2-methyl-benzoyl]amino]-2,4-dimethyl-benzoateYield 44.62%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalyst2×HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of methyl 3-[(5-bromo-2-methyl-benzoyl)amino]-2,4-dimethyl-benzoate (0.5 g, 1.33 mmol), 1,4-dioxa-8-azaspiro(4.5)decane (228.34 mg, 1.59 mmol) and Cs2CO3 (1.3 g, 3.99 mmol) in 1,4-dioxane (10 ml) is added Pd(OAc)2 (29.84 mg, 132.89 μmol) followed by racemic-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (82.75 mg, 132.89 μmol). The reaction mixture is purged with nitrogen for 10 minutes and then heated to 90° C. After 3 hours, very small amount of the product is formed. To the reaction mixture is added Pd(OAc)2 (29.84 mg, 132.89 μmol) followed by racemic-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (82.75 mg, 132.89 μmol) and heated to 100° C. After 12 hours, the reaction is cooled to ambient temperature and diluted with water and extracted with EtOAc. The combined organic layers are washed with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The resulting residue is purified by flash chromatography (silica gel) using 0-100% ethyl acetate in hexane to afford the title compound as a brown solid (0.26 g, 44.62%). Mass spectrum (m/z): 439.2 (M+1).

Workup

  1. customThe reaction mixture is purged with nitrogen for 10 minutes
  2. customvery small amount of the product is formed
  3. temperatureheated to 100° C
  4. waitAfter 12 hours
  5. temperaturethe reaction is cooled to ambient temperature
  6. extractionextracted with EtOAc
  7. washThe combined organic layers are washed with brine
  8. dry with materialdried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customThe resulting residue is purified by flash chromatography (silica gel)

Sources & evidence

ORD record
ord-eeb873ea95bd4d349648421a4f61c513
Source dataset
uspto-grants-2014_02
Patent number
US08642768B2

Reaction notes

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