Cesium carbonate → HCID 24800231, compound

HRID 656524Notes

Reaction equation

HRID 656524 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.[CH:29]1(B(O)O)[CH2:31][CH2:30]1.C(=O)([O-])[O-].[Cs+].[Cs+]>C1(C)C=CC=CC=1>[CH:29]1([C:2]2[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=[C:4]([CH2:12][O:13][CH2:14][C:15]3([C:22]4[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=4)[CH2:20][CH2:19][N:18]([CH3:21])[CH2:17][CH2:16]3)[N:3]=2)[CH2:31][CH2:30]1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 2760897Cyclopropylboronic acidHCID 24801457HCID 24801457, compound

Product 1

HCID 24800231HCID 24800231, compoundYield 68.7%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

2-chloro-6-(((4-(4-fluorophenyl)-1-methylpiperidin-4-yl)methoxy)methyl)-4-(trifluoromethyl)pyridine (50 mg, 0.120 mmol), cyclopropylboronic acid (30.9 mg, 0.360 mmol) PdCl2(dppf)-CH2Cl2Adduct (9.80 mg, 0.012 mmol), cesium carbonate (121 mg, 0.372 mmol) were combined in toluene (1 ml). The reaction was flushed with nitrogen and heated to 100° C. for 2 hours. After cooling, the reaction was quenched with 10 ml saturated sodium bicarbonate, and diluted with ethyl acetate. The organics were then washed with brine, dried over sodium sulfate, filtered, and concentrated in vacuo. The resulting oil was purified via preparatory HPLC and the desired product (34.8 mg, 0.082 mmol, 68.7%) was submitted as the TFA salt. 1H-NMR (CD3OD, 400 MHz) δ 7.48 (m, 2H), 7.33 (m, 1H), 7.14 (t, 2H), 7.08 (m, 1H), 4.47 (m, 2H), 3.46 (m, 4H), 2.84 (m, 2H), 2.74 (s, 3H), 2.67 (m, 2H), 2.13 (m, 3H), 0.97 (m, 4H). LC: Tr=1.850 min, HPLC Method 1. Mass spec.: 423.27 (MH)+.

Workup

  1. customThe reaction was flushed with nitrogen
  2. temperatureAfter cooling
  3. customthe reaction was quenched with 10 ml saturated sodium bicarbonate
  4. additiondiluted with ethyl acetate
  5. washThe organics were then washed with brine
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe resulting oil was purified via preparatory HPLC

Sources & evidence

ORD record
ord-d6a67762bdac473b9faa7ff173a04709
Source dataset
uspto-grants-2011_12
Patent number
US08071778B2

Reaction notes

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