tert-Butyl acetate → 4-Cyano-5-(6-ethoxy-2'-fluoro-4-nitro-biphenyl-3-yl)-3-(tetrahydro-pyran-4-yl)-pent-4-enoic acid tert-butyl ester

HRID 506849Notes

Reaction equation

HRID 506849 reaction equation
[C:1]([O:4][C:5]([CH3:8])([CH3:7])[CH3:6])(=[O:3])[CH3:2].[Li+].C[Si]([N-][Si](C)(C)C)(C)C.C(OP([C:27]([C:35]#[N:36])=[CH:28][CH:29]1[CH2:34][CH2:33][O:32][CH2:31][CH2:30]1)(=O)OCC)C.[CH2:37]([O:39][C:40]1[C:45]([C:46]2[CH:51]=[CH:50][CH:49]=[CH:48][C:47]=2[F:52])=[CH:44][C:43]([CH:53]=O)=[C:42]([N+:55]([O-:57])=[O:56])[CH:41]=1)[CH3:38]>C1COCC1.[Cu]I.C(OCC)(=O)C>[C:5]([O:4][C:1](=[O:3])[CH2:2][CH:28]([CH:29]1[CH2:30][CH2:31][O:32][CH2:33][CH2:34]1)[C:27]([C:35]#[N:36])=[CH:53][C:43]1[CH:44]=[C:45]([C:46]2[CH:51]=[CH:50][CH:49]=[CH:48][C:47]=2[F:52])[C:40]([O:39][CH2:37][CH3:38])=[CH:41][C:42]=1[N+:55]([O-:57])=[O:56])([CH3:8])([CH3:7])[CH3:6]

Participants

8

Reactant 4

HCID 10908tert-Butyl acetateHCID 2733832Lithium HexamethyldisilazideHCID 72481733[1-Cyano-2-(tetrahydro-pyran-4-yl)-vinyl]-phosphonic acid diethyl esterHCID 866341916-Ethoxy-2'-fluoro-4-nitro-biphenyl-3-carbaldehyde

Product 1

HCID 684708434-Cyano-5-(6-ethoxy-2'-fluoro-4-nitro-biphenyl-3-yl)-3-(tetrahydro-pyran-4-yl)-pent-4-enoic acid tert-butyl ester

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of tert-butyl acetate (217 μL, 1.6 mmol) in THF (0.92 mL) at −78° C., LHMDS (1.0 M in THF, 1.4 mL) was added slowly. After 30 min of stirring at −78° C., [1-cyano-2-(tetrahydro-pyran-4-yl)-vinyl]-phosphonic acid diethyl ester (302 mg, 1.1 mmol) dissolved in THF (0.92 mL) was added, followed by CuI (6.3 mg, 0.03 mmol). The resulting solution was warmed to room temperature, stirred for 2 h, and then 6-ethoxy-2′-fluoro-4-nitro-biphenyl-3-carbaldehyde (266.0 mg, 0.9195 mmol), prepared as in Step C above, was added. The resulting solution was stirred at room temperature for another 20 h. Ethyl acetate was then added, and the resulting solution was washed with hydrochloric acid solution (1.0 M) two times and with brine one time, and then dried over magnesium sulfate. The resulting solution was filtered and concentrated. The residue was purified on a silica gel column eluted with a solvent mixture of ethyl acetate and heptanes from 0:100 to 25:75 to yield a residue.

Workup

  1. additionwas added
  2. temperatureThe resulting solution was warmed to room temperature
  3. stirringstirred for 2 h
  4. additionwas added
  5. stirringThe resulting solution was stirred at room temperature for another 20 h
  6. washthe resulting solution was washed with hydrochloric acid solution (1.0 M) two times and with brine one time
  7. dry with materialdried over magnesium sulfate
  8. filtrationThe resulting solution was filtered
  9. concentrationconcentrated
  10. customThe residue was purified on a silica gel column
  11. washeluted with a solvent mixture of ethyl acetate and heptanes from 0:100 to 25:75
  12. customto yield a residue

Sources & evidence

ORD record
ord-6cf81ea46b3f48ae84baecb516740ad1
Source dataset
uspto-grants-2010_08
Patent number
US07786116B2

Reaction notes

Loading…