Ammonium Chloride → (+/-)-(3aR*,7aS*)-7a-(4-bromothiophen-2-yl)-hexahydropyrano[3,4-c]isoxazole

HRID 217999Notes

Reaction equation

HRID 217999 reaction equation
C([Li])CCC.Br[C:7]1[S:8][CH:9]=[C:10]([Br:12])[CH:11]=1.[N:13]1[O:14][CH2:15][CH:16]2[CH2:21][CH2:20][O:19][CH2:18][C:17]=12.[Cl-].[NH4+]>C1(C)C=CC=CC=1.C1COCC1>[Br:12][C:10]1[CH:11]=[C:7]([C@@:17]23[CH2:18][O:19][CH2:20][CH2:21][C@H:16]2[CH2:15][O:14][NH:13]3)[S:8][CH:9]=1

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 2724560Thiophene, 2,4-dibromo-HCID 574756753,3a,4,5-tetrahydro-7H-pyrano[3,4-c]isoxazoleHCID 178418339Butyllithium

Product 1

HCID 68587825(+/-)-(3aR*,7aS*)-7a-(4-bromothiophen-2-yl)-hexahydropyrano[3,4-c]isoxazole

Reagents, catalysts & solvents 1

HCID 22635083Tetrahydrofuran tolueneSolvent2×

Procedure

n-Butyllithium (2.63 M, 2.99 ml) was added dropwise to a solution of 2,4-dibromothiophene (2.00 g) in toluene-THF (10:1) (22 ml) at −78° C. After stirring at the same temperature for one hour, a solution of (±)-3,3a,4,5-tetrahydro-7H-pyrano[3,4-c]isoxazole obtained in Preparation Example 1-(2) (500 mg) in toluene-THF (10:1) (10 ml) and a boron trifluoride-diethyl ether complex (990 μl) were added dropwise at the same time. After stirring at the same temperature for two hours, an ammonium chloride solution was added to terminate the reaction. The aqueous layer was extracted with ethyl acetate, and the organic layer was dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the residue was purified by silica gel column chromatography to obtain the title compound (700 mg).

Workup

  1. additiona boron trifluoride-diethyl ether complex (990 μl) were added dropwise at the same time
  2. stirringAfter stirring at the same temperature for two hours
  3. customto terminate
  4. customthe reaction
  5. extractionThe aqueous layer was extracted with ethyl acetate
  6. dry with materialthe organic layer was dried over anhydrous magnesium sulfate
  7. customThe solvent was evaporated under reduced pressure
  8. customthe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-890d4fed85954240810fff31d0d6b694
Source dataset
uspto-grants-2012_06
Patent number
US08198269B2

Reaction notes

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