Lithium Chloride → 3-[2-Methoxy-3-methoxymethoxymethyl-6-(trimethylsilanyl)pyridin-4-yl]pent-2-enoic acid ethyl ester

HRID 2086337Notes

Reaction equation

HRID 2086337 reaction equation
[Li+].[Cl-].I[C:4]1[CH:9]=[C:8]([Si:10]([CH3:13])([CH3:12])[CH3:11])[N:7]=[C:6]([O:14][CH3:15])[C:5]=1[CH2:16][O:17][CH2:18][O:19][CH3:20].C([Sn](CCCC)(CCCC)/[C:26](/[CH2:33][CH3:34])=[CH:27]/[C:28]([O:30][CH2:31][CH3:32])=[O:29])CCC>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Cu].CS(C)=O>[CH2:31]([O:30][C:28](=[O:29])[CH:27]=[C:26]([C:4]1[CH:9]=[C:8]([Si:10]([CH3:13])([CH3:12])[CH3:11])[N:7]=[C:6]([O:14][CH3:15])[C:5]=1[CH2:16][O:17][CH2:18][O:19][CH3:20])[CH2:33][CH3:34])[CH3:32]

Participants

7

Reactant 3

HCID 433294Lithium ChlorideHCID 10002008ethyl (E)-3-(tributylstannyl)-2-pentenoateHCID 111881914-Iodo-2-methoxy-3-methoxymethoxymethyl-6-(trimethylsilanyl)pyridine

Product 1

HCID 698893403-[2-Methoxy-3-methoxymethoxymethyl-6-(trimethylsilanyl)pyridin-4-yl]pent-2-enoic acid ethyl esterYield 80%

Reagents, catalysts & solvents 3

HCID 62652Cuprous chlorideCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
60 °C

Procedure

A round bottom flask was charged with LiCl (66.6 mg, 1.57 mmol) and flamed dried under vacuum. Pd(PPh3)4 (32.6 mg, 0.026 mmol), CuCl (129.6 mg, 1.31 mmol) and DMSO (2.0 mL) were added and the mixture was degassed. 3a (100 mg, 0.262 mmol) was added, followed by ethyl (E)-3-(tri-n-butylstannyl)-2-pentenoate (131.4 mg, 0.314 mmol) and the resulting mixture was degassed. See Piers, E., et al., Can. J. Chem., 2058 (1992). The reaction mixture was then heated at 60° C. for 17 h. After cooling, the reaction was diluted with Et2O (30 mL) and washed with a mixture of brine (40 mL) and 5% aq. NH4OH (8 mL). The aqueous layer was extracted 3 times with Et2O. The combined organic extracts were dried over MgSO4 and concentrated under reduced pressure. The crude product was purified by flash chromatography (gradient hexane to hexane-EtOAc 95:5) to yield 4a (80 mg, 80%) as a clear oil. 1H NMR (300 MHz, CDCl3) δ0.28 (s, 3H), 0.99 (t, J=7.5 Hz, 3H), 1.3 (t, J=7.1 Hz, 3H), 2.98 (q, J=7.5 Hz, 2H), 3.42 (s, 3H), 4.02 (s, 3H), 4.2 (q, J=7.1 Hz, 2H), 4.47 (s, 2H), 4.72 (s, 2H), 5.79 (s, 1H), 6.84 (s, 1H); 13C NMR (75 MHz, CDCl3) δ−1.96, 12.3, 14.25, 26.57, 53.58, 55.35, 60.01, 61.95, 9672, 115.49, 119.49, 121.17, 151.15, 159.9, 162.21, 164.81, 165.83; IR (film, NaCl, cm−1) 2; LRMS (70 eV, EI) m/z (rel int %) 381 (M+), 366, 336, 320, 308 (100), 290, 262, 246, 89, 73. HRMS m/z calcd for C19H31NO5Si (M+) 381.1976, found 381.19667.

Workup

  1. temperatureflamed
  2. customdried under vacuum
  3. customthe mixture was degassed
  4. customthe resulting mixture was degassed
  5. temperatureAfter cooling
  6. additionthe reaction was diluted with Et2O (30 mL)
  7. washwashed with a mixture of brine (40 mL) and 5% aq. NH4OH (8 mL)
  8. extractionThe aqueous layer was extracted 3 times with Et2O
  9. dry with materialThe combined organic extracts were dried over MgSO4
  10. concentrationconcentrated under reduced pressure
  11. customThe crude product was purified by flash chromatography (gradient hexane to hexane-EtOAc 95:5)

Sources & evidence

ORD record
ord-a52ca348e4e042649484f4f17a99bedf
Source dataset
uspto-grants-2004_04
Patent number
US06723853B2

Reaction notes

Loading…