Cesium carbonate → HCID 44194571, compound

HRID 1192920Notes

Reaction equation

HRID 1192920 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]([N:10]2[CH2:15][CH2:14][C@:13]([CH2:22][CH2:23][OH:24])([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[CH2:12][C:11]2=[O:25])[CH3:9])=[CH:4][CH:3]=1.[F:26][C:27]1[CH:32]=[CH:31][C:30](B(O)O)=[CH:29][CH:28]=1.C([O-])([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>[F:26][C:27]1[CH:32]=[CH:31][C:30]([C:2]2[CH:7]=[CH:6][C:5]([C@@H:8]([N:10]3[CH2:15][CH2:14][C@:13]([CH2:22][CH2:23][OH:24])([C:16]4[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=4)[CH2:12][C:11]3=[O:25])[CH3:9])=[CH:4][CH:3]=2)=[CH:29][CH:28]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 2856454-Fluorophenylboronic acidHCID 44123674HCID 44123674, compound

Product 1

HCID 44194571HCID 44194571, compoundYield 10%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

A mixture of (R)-1-((S)-1-(4-bromophenyl)ethyl)-4-(2-hydroxyethyl)-4-phenyl piperidin-2-one (30 mg, 0.072 mmol), 4-fluorophenylboronic acid (15 mg, 0.11 mmol), Pd(Ph3P)2Cl2 (5 mg), and aqueous Cs2CO3 (0.1 mL, 2M) in 1,4-dioxane (2 mL) was stirred and heated at reflux for 2 h. The organic phase was separated, and concentrated to give the crude product, which was purified by preparative TLC to give (R)-1-((S)-1-(4′-fluorobiphenyl-4-yl)ethyl)-4-(2-hydroxyethyl)-4-phenylpiperidin-2-one (3.0 mg, 10%). LC-MS Method 2, tR=2.103 min, m/z=440.1. 1H NMR (CDCl3): δ 1.46 (d, 3H), 1.83 (m, 1H), 2.01 (m, 3H), 2.32 (m, 1H), 2.59 (dd, 1H), 2.96 (m, 1H), 3.11 (dd, 1H), 3.34 (m, 1H), 3.49 (m, 1H), 6.02 (q, 1H), 6.89 (m, 2H), 7.06 (m, 2H), 7.22 (m, 2H), 7.31 (m, 4H), 7.40 (m, 2H).

Workup

  1. temperatureheated
  2. temperatureat reflux for 2 h
  3. customThe organic phase was separated
  4. concentrationconcentrated
  5. customto give the crude product, which
  6. customwas purified by preparative TLC

Sources & evidence

ORD record
ord-448d68c6c3f743c6a934feafc0bf5feb
Source dataset
uspto-grants-2014_03
Patent number
US08680281B2

Reaction notes

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