Potassium Phosphate, Tribasic → tert-butyl [(1S)-2-({6-[6-(cyclopropylmethoxy)-1,3-benzoxazol-2-yl]pyridin-3-yl}oxy)-1-methylethyl]carbamate

HRID 1026204Notes

Reaction equation

HRID 1026204 reaction equation
[CH:1]1([CH2:4][O:5][C:6]2[CH:14]=[CH:13][C:9]3[N:10]=[CH:11][O:12][C:8]=3[CH:7]=2)[CH2:3][CH2:2]1.Br[C:16]1[N:21]=[CH:20][C:19]([O:22][CH2:23][C@@H:24]([NH:26][C:27](=[O:33])[O:28][C:29]([CH3:32])([CH3:31])[CH3:30])[CH3:25])=[CH:18][CH:17]=1.C(P(C12CC3CC(CC(C3)C1)C2)C12CC3CC(CC(C3)C1)C2)CCC.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CN1CCCC1=O>[CH:1]1([CH2:4][O:5][C:6]2[CH:14]=[CH:13][C:9]3[N:10]=[C:11]([C:16]4[N:21]=[CH:20][C:19]([O:22][CH2:23][C@@H:24]([NH:26][C:27](=[O:33])[O:28][C:29]([CH3:32])([CH3:31])[CH3:30])[CH3:25])=[CH:18][CH:17]=4)[O:12][C:8]=3[CH:7]=2)[CH2:2][CH2:3]1

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 11371790Bis(adamantan-1-yl)(butyl)phosphaneHCID 677784246-(Cyclopropylmethoxy)-1,3-benzoxazoleHCID 86666261tert-butyl {(1S)-2-[(6-bromopyridin-3-yl)oxy]-1-methylethyl}carbamate

Product 1

HCID 86666262tert-butyl [(1S)-2-({6-[6-(cyclopropylmethoxy)-1,3-benzoxazol-2-yl]pyridin-3-yl}oxy)-1-methylethyl]carbamateYield 34.4%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
125 °C

Procedure

A mixture of 6-(cyclopropylmethoxy)-1,3-benzoxazole (500 mg), tert-butyl {(1S)-2-[(6-bromopyridin-3-yl)oxy]-1-methylethyl}carbamate (1.31 g), palladium(II) acetate (29 mg), butyldi(1-adamantyl)phosphine (93 mg), tripotassium phosphate (1.12 g) and N-methylpyrrolidone (12 mL) was stirred under an argon atmosphere at 125° C. for 15 hr. The reaction mixture was allowed to cool to room temperature, and filtered through celite. The filtrate was diluted with ethyl acetate and water, and the organic layer was separated. The combined organic layer was washed with saturated brine, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate) to give the title compound (400 mg).

Workup

  1. temperatureto cool to room temperature
  2. filtrationfiltered through celite
  3. additionThe filtrate was diluted with ethyl acetate and water
  4. customthe organic layer was separated
  5. washThe combined organic layer was washed with saturated brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. customthe solvent was evaporated under reduced pressure
  8. customThe residue was purified by silica gel column chromatography (hexane/ethyl acetate)

Sources & evidence

ORD record
ord-cf87df726f16492d95136896b423f8ec
Source dataset
uspto-grants-2014_05
Patent number
US08729102B2

Reaction notes

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