Trifluoroacetic acid → HCID 24801273, compound

HRID 656522Notes

Reaction equation

HRID 656522 reaction equation
Cl[C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=[C:4]([CH2:12][O:13][CH2:14][C:15]2([C:22]3[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=3)[CH2:20][CH2:19][N:18]([CH3:21])[CH2:17][CH2:16]2)[N:3]=1.[CH3:29]B1OB(C)OB(C)O1.[OH-].[K+].C(O)(C(F)(F)F)=O>O1CCCC1.C(OCC)(=O)C>[F:28][C:25]1[CH:26]=[CH:27][C:22]([C:15]2([CH2:14][O:13][CH2:12][C:4]3[CH:5]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:7]=[C:2]([CH3:29])[N:3]=3)[CH2:20][CH2:19][N:18]([CH3:21])[CH2:17][CH2:16]2)=[CH:23][CH:24]=1

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 14797Potassium HydroxideHCID 574072TrimethylboroxineHCID 24801457HCID 24801457, compound

Product 1

HCID 24801273HCID 24801273, compoundYield 39.7%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

2-chloro-6-(((4-(4-fluorophenyl)-1-methylpiperidin-4-yl)methoxy)methyl)-4-(trifluoromethyl)pyridine (80 mg, 0.192 mmol), tetrakis(triphenylphsophine)palladium(O) (22.18 mg, 0.019 mmol), and 2,4,6-trimethyl-1,3,5,2,4,6-trioxatriborinane (72.3 mg, 0.576 mmol) were combined in tetrahydrofuran (1.5 mL). The reaction was then treated with potassium hydroxide (0.392 ml, 0.392 mmol) and heated to 100° C. for 2 hours. After cooling, the solution was diluted with ethyl acetate (25 mL), washed with water (10 mL) and brine (10 mL). The organics were dried over sodium sulfate, filtered, and concentrated in vacuo. The resulting oil was purified via preparatory HPLC to yield the desired product (30.23 mg, 0.076 mmol, 39.7%) as the TFA salt. 1H-NMR (CDCl3, 400 MHz) δ 10.02 (s, 1H), 8.09 (s, 1H), 7.93 (s, 1H). LC: Tr=1.920 min, HPLC Method 1. Mass spec.: 397.03 (MH)+.

Workup

  1. temperatureAfter cooling
  2. washwashed with water (10 mL) and brine (10 mL)
  3. dry with materialThe organics were dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe resulting oil was purified via preparatory HPLC

Sources & evidence

ORD record
ord-27b086ef8a034bc3a8086b8137b30d03
Source dataset
uspto-grants-2011_12
Patent number
US08071778B2

Reaction notes

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