Dimethylformamide → tert-butyl [(1S)-1-methyl-2-({6-[6-(2-oxopropoxy)-1,3-benzoxazol-2-yl]pyridin-3-yl}oxy)ethyl]carbamate

HRID 1026345Notes

Reaction equation

HRID 1026345 reaction equation
[OH:1][C:2]1[CH:28]=[CH:27][C:5]2[N:6]=[C:7]([C:9]3[N:14]=[CH:13][C:12]([O:15][CH2:16][C@@H:17]([NH:19][C:20](=[O:26])[O:21][C:22]([CH3:25])([CH3:24])[CH3:23])[CH3:18])=[CH:11][CH:10]=3)[O:8][C:4]=2[CH:3]=1.Br[CH2:30][C:31](=[O:33])[CH3:32].C(=O)([O-])[O-].[K+].[K+].CN(C=O)C>O>[CH3:18][C@H:17]([NH:19][C:20](=[O:26])[O:21][C:22]([CH3:23])([CH3:24])[CH3:25])[CH2:16][O:15][C:12]1[CH:13]=[N:14][C:9]([C:7]2[O:8][C:4]3[CH:3]=[C:2]([O:1][CH2:30][C:31](=[O:33])[CH3:32])[CH:28]=[CH:27][C:5]=3[N:6]=2)=[CH:10][CH:11]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 11715BromoacetoneHCID 136372364tert-butyl [(1S)-2-{[6-(6-hydroxy-1,3-benzoxazol-2-yl)pyridin-3-yl]oxy}-1-methylethyl]carbamate

Product 1

HCID 86666284tert-butyl [(1S)-1-methyl-2-({6-[6-(2-oxopropoxy)-1,3-benzoxazol-2-yl]pyridin-3-yl}oxy)ethyl]carbamate

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

Triethylamine (1.22 ml) was added to a solution of hexachloroethane (648 mg) and triphenylphosphine (862 mg) in acetonitrile (5 mL) at room temperature. The mixture was stirred at room temperature for 10 min. Then a mixture of tert-butyl [(1S)-2-({6-[(2,4-dihydroxyphenyl)carbamoyl]pyridin-3-yl}oxy)-1-methylethyl]carbamate (442 mg) and acetonitrile (5 mL) was added, and the mixture was stirred at room temperature overnight. Water was added, and the mixture was extracted with ethyl acetate. The organic layer was separated, washed with brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate) to give a mixture of tert-butyl [(1S)-2-{[6-(6-hydroxy-1,3-benzoxazol-2-yl)pyridin-3-yl]oxy}-1-methylethyl]carbamate and tert-butyl [(1S)-2-({6-[(2,4-dihydroxyphenyl)carbamoyl]pyridin-3-yl}oxy)-1-methylethyl]carbamate. Triethylamine (1.22 ml) was added to a solution of hexachloroethane (648 mg) and triphenylphosphine (862 mg) in acetonitrile (5 mL) at room temperature. The mixture was stirred at room temperature for 10 min. Then a mixture of tert-butyl [(1S)-2-{[6-(6-hydroxy-1,3-benzoxazol-2-yl)pyridin-3-yl]oxy}-1-methylethyl]carbamate and tert-butyl [(1S)-2-({6-[(2,4-dihydroxyphenyl)carbamoyl]pyridin-3-yl}oxy)-1-methylethyl]carbamate, and acetonitrile (5 mL) were added, and the mixture was stirred at room temperature overnight. Water was added, and the mixture was extracted with ethyl acetate. The organic layer was separated, washed with brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate) to give tert-butyl [(1S)-2-{[6-(6-hydroxy-1,3-benzoxazol-2-yl)pyridin-3-yl]oxy}-1-methylethyl]carbamate (640 mg) as a mixture with impurities. A mixture of tert-butyl [(1S)-2-{[6-(6-hydroxy-1,3-benzoxazol-2-yl)pyridin-3-yl]oxy}-1-methylethyl]carbamate (640 mg, a mixture with impurities), 1-bromopropan-2-one (455 mg), potassium carbonate (459 mg), and DMF (10 mL) was stirred at 60° C. for 1 hr. Water was added, and the mixture was extracted with ethyl acetate. The organic layer was separated, washed with brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate) to give tert-butyl [(1S)-1-methyl-2-({6-[6-(2-oxopropoxy)-1,3-benzoxazol-2-yl]pyridin-3-yl}oxy)ethyl]carbamate (630 mg) as a mixture with impurities. Bis(2-methoxyethyl)aminosulfur trifluoride (0.789 mL) was added to a mixture of tert-butyl [(1S)-1-methyl-2-({6-[6-(2-oxopropoxy)-1,3-benzoxazol-2-yl]pyridin-3-yl}oxy)ethyl]carbamate (630 mg, a mixture with impurities) and toluene (10 mL) at room temperature. The mixture was stirred at 80° C. for 2 hr. Saturated sodium hydrogen carbonate solution was added, and the mixture was extracted with ethyl acetate. The organic layer was separated, washed with brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate) to give the title compound (111 mg) as a white solid.

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. customThe organic layer was separated
  3. washwashed with brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by silica gel column chromatography (hexane/ethyl acetate)

Sources & evidence

ORD record
ord-f364653e3f064dc6838326624938579d
Source dataset
uspto-grants-2014_05
Patent number
US08729102B2

Reaction notes

Loading…