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

HRID 239947Notes

Reaction equation

HRID 239947 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([CH3:24])=[C:6]([CH:23]=1)[C:7]([NH:9][C:10]1[C:20]([CH3:21])=[CH:19][C:13]([C:14]([O:16][CH2:17][CH3:18])=[O:15])=[CH:12][C:11]=1[CH3:22])=[O:8].[O:25]1[C:29]2([CH2:34][CH2:33][NH:32][CH2:31][CH2:30]2)[O:28][CH2:27][CH2:26]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>C1COCC1.CC([O-])=O.CC([O-])=O.[Pd+2]>[O:25]1[C:29]2([CH2:34][CH2:33][N:32]([C:2]3[CH:3]=[CH:4][C:5]([CH3:24])=[C:6]([CH:23]=3)[C:7]([NH:9][C:10]3[C:20]([CH3:21])=[CH:19][C:13]([C:14]([O:16][CH2:17][CH3:18])=[O:15])=[CH:12][C:11]=3[CH3:22])=[O:8])[CH2:31][CH2:30]2)[O:28][CH2:27][CH2:26]1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 674351,4-Dioxa-8-azaspiro(4.5)decaneHCID 634876Binap, (A+-)-HCID 86707333Ethyl 4-[(5-bromo-2-methyl-benzoyl)amino]-3,5-dimethyl-benzoate

Product 1

HCID 86707334Ethyl 4-[[5-(1,4-dioxa-8-azaspiro[4.5]decan-8-yl)-2-methyl-benzoyl]amino]-3,5-dimethyl-benzoateYield 36.3%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of ethyl 4-[(5-bromo-2-methyl-benzoyl)amino]-3,5-dimethyl-benzoate (0.5 g, 1.28 mmol), 1,4-dioxa-8-azaspiro(4.5)decane (0.22 g, 1.54 mmol) and Cs2CO3 (1.25 g, 3.84 mmol) in THF (10 ml) is added Pd(OAc)2 (0.04 g, 0.19 mmol) followed by racemic-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (119.7 mg, 0.19 mmol). The reaction mixture is purged with nitrogen for 5 minutes and then heated at 90° C. After 16 hours, the reaction is cooled to ambient temperature and diluted with ammonium chloride and extracted twice with EtOAc. The combined organic layers are 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 (0.21 g, 36.2%). Mass spectrum (m/z): 453.2 (M+1).

Workup

  1. customThe reaction mixture is purged with nitrogen for 5 minutes
  2. temperaturethe reaction is cooled to ambient temperature
  3. additiondiluted with ammonium chloride
  4. extractionextracted twice with EtOAc
  5. dry with materialThe combined organic layers are dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe resulting residue is purified by flash chromatography (silica gel)

Sources & evidence

ORD record
ord-959afd17c6454dedbf835252ea1a553e
Source dataset
uspto-grants-2014_02
Patent number
US08642768B2

Reaction notes

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