Dimethylacetamide → HCID 58128545, compound

HRID 1798827Notes

Reaction equation

HRID 1798827 reaction equation
Cl[C:2]1[CH:7]=[C:6]([O:8][CH2:9][C:10]2[CH:15]=[CH:14][C:13]([O:16][CH3:17])=[CH:12][CH:11]=2)[N:5]=[C:4]([CH3:18])[N:3]=1.C(P(C(C)(C)C)C1C=CC2C(=CC=CC=2)C=1C1C2C(=CC=CC=2)C=CC=1)(C)(C)C.C[C:49]([N:51](C)C)=O>FC(F)(F)C([O-])=O.[Pd+2].FC(F)(F)C([O-])=O.[Zn].[C-]#N.[Zn+2].[C-]#N>[CH3:17][O:16][C:13]1[CH:14]=[CH:15][C:10]([CH2:9][O:8][C:6]2[N:5]=[C:4]([CH3:18])[N:3]=[C:2]([C:49]#[N:51])[CH:7]=2)=[CH:11][CH:12]=1

Participants

7

Reactant 3

HCID 31374DimethylacetamideHCID 2734941(1,1'-Binaphthalen)-2-yldi-tert-butylphosphineHCID 58128582HCID 58128582, compound

Product 1

HCID 58128545HCID 58128545, compound

Reagents, catalysts & solvents 3

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 23994ZincCatalystHCID 2733347Palladium(II) trifluoroacetateCatalyst

Procedure

The starting 4-chloro-6-[(4-methoxybenzyl)oxy]-2-methylpyrimidine from step 1 of this example (3.7 g 14 mmol), palladium trifluoroacetate (0.2 g, 0.6 mmol), racemic-2-(di-t-butylphosphino)-1,1-binaphthyl ligand (0.49 g, 1.23 mmol), zinc dust (0.17 g, 2.65 mmol) and zinc cyanide (0.92 g, 7.8 mmol) were added to a flask (100 mL), and dimethylacetamide (73 mL) was added. The flask was evacuated and back filled with N2 (3 times), and reaction solution was stirred at room temperature for 30 min. The reaction was then heated to 95° C. for 30 min and monitored until starting material was consumed. The reaction was cooled to room temperature, diluted with ethyl acetate (100 mL), washed with brine (50 mL, ×2), dried over MgSO4, filtered and concentrated i. vac. The crude pale yellow oil was purified by chromatography on silica gel (eluting 7.7% ethyl acetate/hexane) to yield the titled compound as a white solid. LC-MS (M+23): 278.

Workup

  1. additionwas added
  2. customThe flask was evacuated
  3. additionback filled with N2 (3 times), and reaction solution
  4. temperatureThe reaction was then heated to 95° C. for 30 min
  5. customwas consumed
  6. temperatureThe reaction was cooled to room temperature
  7. additiondiluted with ethyl acetate (100 mL)
  8. washwashed with brine (50 mL, ×2)
  9. dry with materialdried over MgSO4
  10. filtrationfiltered
  11. concentrationconcentrated i
  12. customThe crude pale yellow oil was purified by chromatography on silica gel (eluting 7.7% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-725e06c9a48c400782ae90d2fba04ded
Source dataset
uspto-grants-2013_01
Patent number
US08343990B2

Reaction notes

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