Cesium carbonate → HCID 44194658, compound

HRID 1192934Notes

Reaction equation

HRID 1192934 reaction equation
[OH:1][C:2]([CH3:35])([CH3:34])[CH2:3][C@:4]1([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[CH2:9]C[N:7]([C@H:10]([C:12]2[CH:17]=[CH:16][C:15](B3OC(C)(C)C(C)(C)O3)=[CH:14][CH:13]=2)[CH3:11])[C:6](=O)[CH2:5]1.I[C:37]1[CH:42]=[CH:41][N:40]([CH3:43])[C:39](=[O:44])[CH:38]=1.[C:45]([O-:48])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[OH:1][C:2]([CH3:34])([CH3:35])[CH2:3][C@:4]1([C:28]2[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=2)[CH2:5][CH2:6][N:7]([C@H:10]([C:12]2[CH:17]=[CH:16][C:15]([C:37]3[CH:42]=[CH:41][N:40]([CH3:43])[C:39](=[O:44])[CH:38]=3)=[CH:14][CH:13]=2)[CH3:11])[C:45](=[O:48])[CH2:9]1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 534080094-Iodo-1-methylpyridin-2(1H)-oneHCID 58237932HCID 58237932, compound

Product 1

HCID 44194658HCID 44194658, compoundYield 14%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

To a solution of (R)-4-(2-hydroxy-2-methylpropyl)-4-phenyl-1-((S)-1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)ethyl)piperidin-2-one (20 mg, 0.042 mmol) and 4-iodo-1-methylpyridin-2(1H)-one (7.8 mg, 0.084 mmol) in dry 1,4-dioxane (5 mL) was added Cs2CO3 (0.042 mL, 0.084 mmol) and Pd(PPh3)2Cl2 (10 mg). After addition, the mixture was warmed at 110° C. for 2 h under nitrogen. After TLC showed the starting material had disappeared, the solid was filtered off. Water (20 mL) and EtOAc (10 mL) were added, the organic layer was separated, and the aqueous layer was extracted with EtOAc (3×10 mL). The combined organic layers were washed with brine, dried over Na2SO4, filtered, and concentrated to give 4-(4-((S)-1-((R)-4-(2-hydroxy-2-methylpropyl)-2-oxo-4-phenylpiperidin-1-yl)ethyl)phenyl)-1-methylpyridin-2(1H)-one (2.63 mg, 14%), which was purified by preparative HPLC. LC-MS Method 2, tR=1.163 min, m/z=459.2. 1H NMR (CDCl3): δ 0.81 (s, 3H), 0.98 (s, 3H), 1.41 (d, 3H), 1.80 (m, 1H), 1.96 (m, 1H), 1.99-2.18 (m, 4H), 2.58 (m, 1H), 2.87 (m, 1H), 3.47 (m, 1H), 3.57 (s, 3H), 5.95 (m, 1H), 6.41 (m, 1H), 6.80 (s, 1H), 6.91 (m, 2H), 7.18 (m, 1H), 7.24 (m, 6H), 7.32 (d, 1H).

Workup

  1. additionAfter addition
  2. filtrationthe solid was filtered off
  3. additionWater (20 mL) and EtOAc (10 mL) were added
  4. customthe organic layer was separated
  5. extractionthe aqueous layer was extracted with EtOAc (3×10 mL)
  6. washThe combined organic layers were washed with brine
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-281883da396f4ef99318908d954b61dd
Source dataset
uspto-grants-2014_03
Patent number
US08680281B2

Reaction notes

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