Ammonium Chloride → [4-(4-Hydroxy-tetrahydro-pyran-4-yl)-phenyl]carbamic acid tert-butyl ester

HRID 714876Notes

Reaction equation

HRID 714876 reaction equation
[C:1]([O:5][C:6](=[O:15])[NH:7][C:8]1[CH:13]=[CH:12][C:11](Br)=[CH:10][CH:9]=1)([CH3:4])([CH3:3])[CH3:2].C([Li])CCC.[O:21]1[CH2:26][CH2:25][C:24](=[O:27])[CH2:23][CH2:22]1.[Cl-].[NH4+]>O1CCCC1>[C:1]([O:5][C:6](=[O:15])[NH:7][C:8]1[CH:13]=[CH:12][C:11]([C:24]2([OH:27])[CH2:25][CH2:26][O:21][CH2:22][CH2:23]2)=[CH:10][CH:9]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 121599Tetrahydro-4H-pyran-4-oneHCID 27736084-Bromoaniline, N-BOC protectedHCID 178418339Butyllithium

Product 1

HCID 68486334[4-(4-Hydroxy-tetrahydro-pyran-4-yl)-phenyl]carbamic acid tert-butyl esterYield 36.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of tert-butyl(4-bromophenyl)carbamate (1.5 g) in tetrahydrofuran (30 mL) was added dropwise n-butyllithium (1.6 M hexane solution, 7.2 mL) at −78° C. under nitrogen atmosphere, and the mixture was stirred at the same temperature for 1 hr. Dihydro-2H-pyran-4(3H)-one (0.58 g) was added thereto, and the mixture was stirred overnight while it was allowed to be warmed. To the reaction mixture was added saturated aqueous ammonium chloride 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 the title compound (590 mg).

Workup

  1. stirringthe mixture was stirred overnight while it
  2. temperatureto be warmed
  3. extractionthe mixture was extracted with ethyl acetate
  4. washThe obtained organic layer was washed with 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-0cc786585deb4b028302d5a6cc2b7c7b
Source dataset
uspto-grants-2015_11
Patent number
US09187453B2

Reaction notes

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