Hydrochloric Acid → HCID 70865029, compound

HRID 336210Notes

Reaction equation

HRID 336210 reaction equation
[C:1]([C:5]1[O:9][N:8]=[C:7]([NH:10][C:11]([CH:13]2[CH2:18][O:17][CH2:16][CH2:15][NH:14]2)=[O:12])[CH:6]=1)([CH3:4])([CH3:3])[CH3:2].Cl.[F:20][C:21]1([F:30])[CH2:26][CH2:25][CH:24]([C:27](O)=[O:28])[CH2:23][CH2:22]1.C(N(CC)C(C)C)(C)C.P(Cl)(Cl)(Cl)=O>C(#N)C>[C:1]([C:5]1[O:9][N:8]=[C:7]([NH:10][C:11]([CH:13]2[CH2:18][O:17][CH2:16][CH2:15][N:14]2[C:27]([CH:24]2[CH2:25][CH2:26][C:21]([F:30])([F:20])[CH2:22][CH2:23]2)=[O:28])=[O:12])[CH:6]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 24813Phosphorus oxychlorideHCID 81531DiisopropylethylamineHCID 27791364,4-Difluorocyclohexanecarboxylic acidHCID 70865354HCID 70865354, compound

Product 1

HCID 70865029HCID 70865029, compound

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a cold (0° C.) solution of morpholine-3-carboxylic acid (5-tert-butyl-isoxazol-3-yl)-amide; hydrochloride (50 mg; 0.115 mmol), 4,4-difluorocyclohexanecarboxylic acid (18.9 mg, 0.115 mmol) and N,N-diisopropylethylamine (0.052 mL; 0.3 mmol) in anhydrous acetonitrile (2 mL) is added phosphorous oxychloride (0.01 mL; 0.115 mmol). The reaction mixture is left stirring at room temperature for 18 hours. After this time, the reaction mixture is quenched with saturated NH4Cl aqueous solution and extracted with ethyl acetate twice. The organics are combined and washed with brine, dried over Na2SO4, filtered and concentrated under reduced pressure. Purification by preparative LC-MS provides the title compound, m/z 400 [M+H+].

Workup

  1. waitThe reaction mixture is left
  2. customAfter this time, the reaction mixture is quenched with saturated NH4Cl aqueous solution
  3. extractionextracted with ethyl acetate twice
  4. washwashed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customPurification by preparative LC-MS

Sources & evidence

ORD record
ord-24a863d02247428597231e47359f7e18
Source dataset
uspto-grants-2014_11
Patent number
US08889670B2

Reaction notes

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