Bromoacetone → tert-butyl [(1S)-2-({6-[6-(2-fluoropropoxy)-1,3-benzoxazol-2-yl]pyridin-3-yl}oxy)-1-methylethyl]carbamate

HRID 1026290Notes

Reaction equation

HRID 1026290 reaction equation
O[CH:2]([CH3:32])[CH2:3][O:4][C:5]1[CH:31]=[CH:30][C:8]2[N:9]=[C:10]([C:12]3[N:17]=[CH:16][C:15]([O:18][CH2:19][C@@H:20]([NH:22][C:23](=[O:29])[O:24][C:25]([CH3:28])([CH3:27])[CH3:26])[CH3:21])=[CH:14][CH:13]=3)[O:11][C:7]=2[CH:6]=1.OC1C=CC2N=C(C3N=CC(OC[C@@H](NC(=O)OC(C)(C)C)C)=CC=3)OC=2C=1.BrCC(=O)C.COCCN(S(F)(F)[F:76])CCOC.C(=O)([O-])O.[Na+]>C1(C)C=CC=CC=1>[F:76][CH:2]([CH3:32])[CH2:3][O:4][C:5]1[CH:31]=[CH:30][C:8]2[N:9]=[C:10]([C:12]3[N:17]=[CH:16][C:15]([O:18][CH2:19][C@@H:20]([NH:22][C:23](=[O:29])[O:24][C:25]([CH3:28])([CH3:27])[CH3:26])[CH3:21])=[CH:14][CH:13]=3)[O:11][C:7]=2[CH:6]=1

Participants

7

Reactant 5

HCID 11715BromoacetoneHCID 516892Sodium BicarbonateHCID 2734690(Bis(2-methoxyethyl)amino)sulfur trifluorideHCID 86666296tert-butyl [(1S)-2-({6-[6-(2-hydroxypropoxy)-1,3-benzoxazol-2-yl]pyridin-3-yl}oxy)-1-methylethyl]carbamateHCID 136372364tert-butyl [(1S)-2-{[6-(6-hydroxy-1,3-benzoxazol-2-yl)pyridin-3-yl]oxy}-1-methylethyl]carbamate

Product 1

HCID 86666295tert-butyl [(1S)-2-({6-[6-(2-fluoropropoxy)-1,3-benzoxazol-2-yl]pyridin-3-yl}oxy)-1-methylethyl]carbamate

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A mixture of tert-butyl [(1S)-2-({6-[6-(2-hydroxypropoxy)-1,3-benzoxazol-2-yl]pyridin-3-yl}oxy)-1-methylethyl]carbamate (1.02 g) (obtained using tert-butyl [(1S)-2-{[6-(6-hydroxy-1,3-benzoxazol-2-yl)pyridin-3-yl]oxy}-1-methylethyl]carbamate (4.00 g) and 1-bromopropan-2-one (1.56 g) and in the same manner as in Example 2, step E and Example 24, step F), bis(2-methoxyethyl)aminosulfur trifluoride (0.848 mL) and toluene (10 mL) was stirred at room temperature for 1 hr. To the reaction mixture was added saturated aqueous sodium hydrogen carbonate solution, and the mixture was extracted with ethyl acetate. The obtained 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 tert-butyl [(1S)-2-({6-[6-(2-fluoropropoxy)-1,3-benzoxazol-2-yl]pyridin-3-yl}oxy)-1-methylethyl]carbamate. Using the obtained compound, and in the same manner as in Example 1, step D, the title compound was obtained (61.3 mg).

Workup

  1. customobtained
  2. extractionthe mixture was extracted with ethyl acetate
  3. washThe obtained organic layer was washed with saturated brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. customthe solvent was evaporated under reduced pressure
  6. customThe residue was purified by silica gel column chromatography (hexane/ethyl acetate)

Sources & evidence

ORD record
ord-592a0b6d641c45b981a2e57f124291b9
Source dataset
uspto-grants-2014_05
Patent number
US08729102B2

Reaction notes

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