2-(3-Butynyloxy)tetrahydro-2H-pyran → 4-Acetylamino-3-[4-(tetrahydro-pyran-2-yloxy)-but-1-ynyl]-benzoic acid methyl ester

HRID 591693Notes

Reaction equation

HRID 591693 reaction equation
[CH3:1][O:2][C:3](=[O:15])[C:4]1[CH:9]=[CH:8][C:7]([NH:10][C:11](=[O:13])[CH3:12])=[C:6](I)[CH:5]=1.[CH2:16]([O:20][CH:21]1[CH2:26][CH2:25][CH2:24][CH2:23][O:22]1)[CH2:17][C:18]#[CH:19]>CN(C=O)C.C(N(CC)CC)C.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.[Cu]I>[CH3:1][O:2][C:3](=[O:15])[C:4]1[CH:9]=[CH:8][C:7]([NH:10][C:11](=[O:13])[CH3:12])=[C:6]([C:19]#[C:18][CH2:17][CH2:16][O:20][CH:21]2[CH2:26][CH2:25][CH2:24][CH2:23][O:22]2)[CH:5]=1

Participants

7

Reactant 2

HCID 1424402-(3-Butynyloxy)tetrahydro-2H-pyranHCID 15304890Methyl 4-acetamido-3-iodobenzoate

Product 1

HCID 666710504-Acetylamino-3-[4-(tetrahydro-pyran-2-yloxy)-but-1-ynyl]-benzoic acid methyl esterYield 148.8%

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolvent2×HCID 8471TriethylamineSolvent2×

Conditions

Temperature
80 °C

Procedure

To a degassed solution of 4-acetylamino-3-iodo-benzoic acid methyl ester (41.4 g, 130 mmol) in DMF (200 mL) and triethylamine (40 mL) were added PdCl2(PPh3)2 (3.99 g, 5.68 mmol) and copper (I) iodide (7.43 g, 39.0 mmol). A degassed solution of 2-but-3-ynyloxy-tetrahydro-pyran (30.1 g, 195 mmol) in DMF (100 mL) and triethylamine (20 mL) was added at 80° C. over a period of 1 hour under nitrogen. After the addition, the reaction mixture was stirred at 80° C. for 2 hours and then cooled to room temperature. Solvent was evaporated under reduced pressure. Ethyl acetate (200 mL) was added. The solid was filtered, and washed with ethyl acetate. The ethyl acetate solution was washed with brine, and dried over anhydrous Na2SO4. The organic phase was concentrated to dryness, to afford 66.8 g crude 4-acetylamino-3-[4-(tetrahydro-pyran-2-yloxy)-but-1-ynyl]-benzoic acid methyl ester. This was used in next step without further purification.

Workup

  1. additionAfter the addition
  2. temperaturecooled to room temperature
  3. customSolvent was evaporated under reduced pressure
  4. additionEthyl acetate (200 mL) was added
  5. filtrationThe solid was filtered
  6. washwashed with ethyl acetate
  7. washThe ethyl acetate solution was washed with brine
  8. dry with materialdried over anhydrous Na2SO4
  9. concentrationThe organic phase was concentrated to dryness

Sources & evidence

ORD record
ord-1b6b892ccfb64b1e83db426fa2b428a7
Source dataset
uspto-grants-2016_01
Patent number
US09238640B2

Reaction notes

Loading…