Cesium carbonate → 3-(1,4-Dioxa-8-aza-spiro[4.5]dec-8-yl)-4-methyl-benzoic acid methyl ester

HRID 1853948

Reaction equation

HRID 1853948 reaction equation
[O:1]1[C:5]2([CH2:10][CH2:9][NH:8][CH2:7][CH2:6]2)[O:4][CH2:3][CH2:2]1.[CH3:11][O:12][C:13](=[O:22])[C:14]1[CH:19]=[CH:18][C:17]([CH3:20])=[C:16](Br)[CH:15]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>C1(C)C=CC=CC=1>[CH3:11][O:12][C:13](=[O:22])[C:14]1[CH:19]=[CH:18][C:17]([CH3:20])=[C:16]([N:8]2[CH2:9][CH2:10][C:5]3([O:4][CH2:3][CH2:2][O:1]3)[CH2:6][CH2:7]2)[CH:15]=1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 674351,4-Dioxa-8-azaspiro(4.5)decaneHCID 7015747Methyl 3-bromo-4-methylbenzoate

Product 1

HCID 673546753-(1,4-Dioxa-8-aza-spiro[4.5]dec-8-yl)-4-methyl-benzoic acid methyl ester

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A mixture of 2,2′-Bis(diphenylphosphino)1,1′-binaphthyl[BINAP] (54.35 mg, 0.085 mmol) and Palladium(II)acetate[Pd(OAc)2] (6.95 mg, 0.028 mmol) in dry toluene (3 ml) was stirred vigorously and nitrogen was bubbled through the suspension for 30 minutes. To this, 1,4-Dioxa-8-aza-spiro[4.5]-decane (100 mg, 0.699 mmol), 3-Bromo-4-methyl-benzoic acid methyl ester (192.1 mg, 0.839 mmol) and dry Cesium Carbonate (683.5 mg, 2.09 mmol) was added. Nitrogen was bubbled through for another 30 minutes; the mixture was allowed to reflux overnight. The mixture was cooled, diluted with ethylacetate, water was added and the layers separated. The aqueous layer was extracted with ethyl acetate) and the two organic extracts were combined. The organics were washed with brine, then dried (sodium sulfate), filtered and concentrated. Further purification by silica gel chromatography using 5-10% ethyl acetate/Hexane as eluent provided 3-(1,4-Dioxa-8-aza-spiro[4.5]dec-8-yl)-4-methyl-benzoic acid methyl ester [11] as a yellow solid [150.5 mg, 61.7%]

Workup

  1. customnitrogen was bubbled through the suspension for 30 minutes
  2. customNitrogen was bubbled through for another 30 minutes
  3. temperatureto reflux overnight
  4. temperatureThe mixture was cooled
  5. additiondiluted with ethylacetate, water
  6. additionwas added
  7. customthe layers separated
  8. extractionThe aqueous layer was extracted with ethyl acetate) and the two organic extracts
  9. washThe organics were washed with brine
  10. dry with materialdried (sodium sulfate)
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customFurther purification by silica gel chromatography

Sources & evidence

ORD record
ord-f2e0da60e2dd48eeaa25344f32643f4a
Source dataset
uspto-grants-2015_02
Patent number
US08962637B2

Linked notes

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