Cesium carbonate → Tert-butyl 4'-methyl-5-(5-oxa-6-azaspiro[3.4]oct-6-en-7-yl)biphenyl-3-carboxylate

HRID 1257550Notes

Reaction equation

HRID 1257550 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:12]=[C:13]([C:15]2[CH2:22][C:18]3([CH2:21][CH2:20][CH2:19]3)[O:17][N:16]=2)[CH:14]=1)[C:5]([O:7][C:8]([CH3:11])([CH3:10])[CH3:9])=[O:6].[CH3:23][C:24]1[CH:29]=[CH:28][C:27](B(O)O)=[CH:26][CH:25]=1.C(=O)([O-])[O-].[Cs+].[Cs+].C([O-])(O)=O.[Na+]>C1COCC1.O.C1C=CC([PH+]([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C1C=CC([PH+]([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C(Cl)Cl.Cl[Pd]Cl.[Fe]>[CH3:23][C:24]1[CH:29]=[CH:28][C:27]([C:2]2[CH:14]=[C:13]([C:15]3[CH2:22][C:18]4([CH2:21][CH2:20][CH2:19]4)[O:17][N:16]=3)[CH:12]=[C:4]([C:5]([O:7][C:8]([CH3:11])([CH3:10])[CH3:9])=[O:6])[CH:3]=2)=[CH:26][CH:25]=1

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 79799Tolylboronic acidHCID 516892Sodium BicarbonateHCID 58096138Tert-butyl 3-bromo-5-(5-oxa-6-azaspiro[3.4]oct-6-en-7-yl)benzoate

Product 1

HCID 66895976Tert-butyl 4'-methyl-5-(5-oxa-6-azaspiro[3.4]oct-6-en-7-yl)biphenyl-3-carboxylateYield 90%

Reagents, catalysts & solvents 3

HCID 53485975CID 53485975CatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
120 °C

Procedure

To a solution of tert-butyl 3-bromo-5-(5-oxa-6-azaspiro[3.4]oct-6-en-7-yl)benzoate (1.36 g, 3.71 mmol) in THF (8 mL) and water (8 mL) were added (4-methylphenyl)boronic acid (1.01 g, 7.43 mmol), dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium(II) dichloromethane adduct (82 mg, 0.11 mmol) and cesium carbonate (3.63 g, 11.1 mmol). The mixture was heated to 120° C. in a microwave reactor for 10 min. The mixture was cooled to ambient temperature and saturated aqueous NaHCO3 was added and the mixture was extracted with ethyl acetate (3×). The combined organic extracts were washed with water (2×), brine, dried over sodium sulfate, filtered and concentrated. Purification by silica gel chromatography (100% hexanes 85% hexanes/ethyl acetate) gave the title compound (1.26 g). MS 378.3 (M+1).

Workup

  1. temperatureThe mixture was cooled to ambient temperature
  2. extractionthe mixture was extracted with ethyl acetate (3×)
  3. washThe combined organic extracts were washed with water (2×), brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customPurification by silica gel chromatography (100% hexanes 85% hexanes/ethyl acetate)

Sources & evidence

ORD record
ord-78921ca86f4b44288516dffc2e7b3b40
Source dataset
uspto-grants-2013_06
Patent number
US08461185B2

Reaction notes

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