Ammonium Chloride → HCID 86685862, compound

HRID 1629772Notes

Reaction equation

HRID 1629772 reaction equation
[F:1][C:2]([F:22])([F:21])[CH2:3][CH2:4][CH2:5][O:6][C:7]1[CH:12]=[CH:11][C:10](/[C:13](/[CH3:20])=[CH:14]/[C:15]([O:17]CC)=O)=[CH:9][CH:8]=1.Cl.[CH3:24][NH:25][O:26][CH3:27].C(Cl)(Cl)Cl.C(=O)=O.C([Mg]Cl)(C)C.[NH4+].[Cl-]>C1COCC1.O>[CH3:27][O:26][N:25]([CH3:24])[C:15](=[O:17])/[CH:14]=[C:13](/[C:10]1[CH:9]=[CH:8][C:7]([O:6][CH2:5][CH2:4][CH2:3][C:2]([F:1])([F:21])[F:22])=[CH:12][CH:11]=1)\[CH3:20]

Participants

8

Reactant 5

HCID 25517Ammonium ChlorideHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 86583683HCID 86583683, compoundHCID 86685861HCID 86685861, compoundHCID 178418918HCID 178418918, compound

Product 1

HCID 86685862HCID 86685862, compoundYield 58%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-61 °C

Procedure

A solution of Intermediate 11B (2.67 g, 8.44 mmol) and N,O-dimethylhydroxylamine hydrochloride (1.65 g, 16.9 mmol) in anhydrous THF (35 mL) was cooled to −61° C. (CHCl3/dry ice) under an atmosphere of Ar. To this solution was added 0.5 M isopropylmagnesium chloride (16.9 mL, 33.8 mmol) in THF slowly via a syringe. The reaction was stirred at −61° C. for 1.5 h, warmed to −20° C. (sat'd aq NaCl/ice) and stirred for 40 min, then warmed to 0° C. and stirred for 20 min. The reaction was poured into 10 mL of sat'd aq NH4Cl and 12 mL of water, and then extracted with EtOAc. The organic layer was washed with sat'd aq NaCl, dried over anhydrous MgSO4, filtered and concentrated. The residue was purified by silica gel chromatography eluting with EtOAc in hexanes to provide Intermediate 11C (1.62 g, 58%) as a light brown oil. LCMS Anal. Calc'd for C16H20F3NO3 331.33, found [M+H] 332.2.

Workup

  1. stirringstirred for 40 min
  2. temperaturewarmed to 0° C.
  3. stirringstirred for 20 min
  4. extractionextracted with EtOAc
  5. washThe organic layer was washed with sat'd aq NaCl
  6. dry with materialdried over anhydrous MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by silica gel chromatography
  10. washeluting with EtOAc in hexanes

Sources & evidence

ORD record
ord-c318d896275d4175830c9fdb5b313479
Source dataset
uspto-grants-2014_07
Patent number
US08791091B2

Reaction notes

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