Ammonium Chloride → HCID 57827394, compound

HRID 2281843Notes

Reaction equation

HRID 2281843 reaction equation
C([Li])CCC.Br[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1[F:13].[N:14]1[O:15][CH2:16][CH:17]2[CH2:21][O:20][CH2:19][C:18]=12.FC1C=CC=CC=1[Li].[Cl-].[NH4+]>CCCCCC.C1COCC1.C1(C)C=CC=CC=1.C1(C)C=CC=CC=1.CCOC(C)=O.O>[F:13][C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=1[C@:18]12[CH2:19][O:20][CH2:21][C@H:17]1[CH2:16][O:15][NH:14]2

Participants

11

Reactant 5

HCID 25517Ammonium ChlorideHCID 612591-Bromo-2-fluorobenzeneHCID 57827173HCID 57827173, compoundHCID 178418339ButyllithiumHCID 178506686HCID 178506686, compound

Product 1

HCID 57827394HCID 57827394, compoundYield 63.1%

Reagents, catalysts & solvents 5

HCID 962WaterSolventHCID 1140TolueneSolventHCID 8058HexaneSolventHCID 8857Ethyl AcetateSolventHCID 22635083Tetrahydrofuran tolueneSolvent

Procedure

A 2.77 M solution of n-butyllithium in hexane (30.7 mL) was added dropwise to a solution containing 2-bromofluorobenzene (15.6 g) in THF/toluene (50 mL/150 mL) under a nitrogen atmosphere at −78° C. The reaction solution was stirred at the same temperature for 1 h. A boron trifluoride-diethyl ether complex (10.7 mL) was added dropwise to a solution containing (±)-3a,4-dihydro-3H,6H-furo[3,4-c]isoxazole (4.8 g) in toluene (350 mL) under a nitrogen atmosphere at −78° C. Previously prepared 2-fluorophenyllithium was added dropwise to the reaction solution at the same temperature. After stirring at the same temperature for 1 h, aqueous ammonium chloride was added to the reaction solution, and the reaction solution was warmed to RT. Water and EtOAc were added to the reaction solution, and the organic layer was separated. The organic layer was washed with a saturated sodium chloride solution. The organic layer was dried over anhydrous MgSO4, and the insoluble matter was separated by filtration. The filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography to obtain the title compound (5.6 g). 1H NMR (400 MHz, CDCl3) δ ppm 3.39-3.45 (m, 1H), 3.52-3.62 (brm, 1H), 3.84-3.92 (brm, 2H), 3.98 (brd, J=9.2 Hz, 1H), 4.16 (ddd, J=2.4, 6.4, 11.2 Hz, 1H), 4.50-4.58 (brm, 1H), 5.11 (brs, 1H), 7.06 (ddd, J=1.2, 8.4, 11.6 Hz, 1H), 7.16 (ddd, J=1.2, 7.6, 7.6 Hz, 1H), 7.25-7.31 (m, 1H), 7.84-7.95 (m, 1H).

Workup

  1. additionA boron trifluoride-diethyl ether complex (10.7 mL) was added dropwise to a solution
  2. stirringAfter stirring at the same temperature for 1 h
  3. customthe organic layer was separated
  4. washThe organic layer was washed with a saturated sodium chloride solution
  5. dry with materialThe organic layer was dried over anhydrous MgSO4
  6. customthe insoluble matter was separated by filtration
  7. concentrationThe filtrate was concentrated under reduced pressure
  8. customThe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-a69207a2389b45928d5849ec7fdfff36
Source dataset
uspto-grants-2015_09
Patent number
US09139594B2

Reaction notes

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