Hydrochloric Acid → tert-butyl [(1S)-2-({5-[5-(cyclopropylmethoxy)-1,3-benzoxazol-2-yl]-4-methylisoxazol-3-yl}oxy)-1-methylethyl]carbamate

HRID 1026237Notes

Reaction equation

HRID 1026237 reaction equation
[CH:1]1([CH2:4][O:5][C:6]2[CH:7]=[CH:8][C:9]3[O:13][C:12]([C:14]4[O:18][N:17]=[C:16]([O:19][CH2:20][C@@H:21]([NH:23][C:24](=[O:30])[O:25][C:26]([CH3:29])([CH3:28])[CH3:27])[CH3:22])[CH:15]=4)=[N:11][C:10]=3[CH:31]=2)[CH2:3][CH2:2]1.[CH2:32]([Li])CCC.IC.Cl>C1COCC1.CCCCCC>[CH:1]1([CH2:4][O:5][C:6]2[CH:7]=[CH:8][C:9]3[O:13][C:12]([C:14]4[O:18][N:17]=[C:16]([O:19][CH2:20][C@@H:21]([NH:23][C:24](=[O:30])[O:25][C:26]([CH3:27])([CH3:29])[CH3:28])[CH3:22])[C:15]=4[CH3:32])=[N:11][C:10]=3[CH:31]=2)[CH2:2][CH2:3]1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 6328Methyl iodideHCID 86666265tert-butyl [(1S)-2-({5-[5-(cyclopropylmethoxy)-1,3-benzoxazol-2-yl]isoxazol-3-yl}oxy)-1-methylethyl]carbamateHCID 178418339Butyllithium

Product 1

HCID 86666270tert-butyl [(1S)-2-({5-[5-(cyclopropylmethoxy)-1,3-benzoxazol-2-yl]-4-methylisoxazol-3-yl}oxy)-1-methylethyl]carbamate

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8058HexaneSolvent

Conditions

Temperature
-78 °C

Procedure

Under an argon atmosphere, to a solution of tert-butyl [(1S)-2-({5-[5-(cyclopropylmethoxy)-1,3-benzoxazol-2-yl]isoxazol-3-yl}oxy)-1-methylethyl]carbamate (644 mg) in THF (15 mL) was added dropwise a hexane solution (1.6 M, 2.156 mL) of n-butyllithium at −78° C., and the mixture was stirred at −78° C. for 20 min. To the reaction mixture was added iodomethane (0.140 mL), and the mixture was stirred at −78° C. for 15 min, and then at 0° C. for 1 hr. The reaction mixture was neutralized with 1M hydrochloric acid, and extracted with ethyl acetate. The combined organic layer was washed with water and 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 (46.0 mg).

Workup

  1. stirringthe mixture was stirred at −78° C. for 15 min
  2. waitat 0° C. for 1 hr
  3. extractionextracted with ethyl acetate
  4. washThe combined organic layer was washed with water and saturated brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. customthe solvent was evaporated under reduced pressure
  7. customThe residue was purified by silica gel column chromatography (hexane/ethyl acetate)

Sources & evidence

ORD record
ord-ff3fb5612c234c8ab21afe6f2c37c89c
Source dataset
uspto-grants-2014_05
Patent number
US08729102B2

Reaction notes

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