1,4-Dioxane → HCID 66749676, compound

HRID 2402124Notes

Reaction equation

HRID 2402124 reaction equation
Br[C:2]1[S:3][C:4]([C:15]([O:17][CH2:18][CH3:19])=[O:16])=[C:5]([CH2:7][C:8]2[CH:13]=[CH:12][C:11]([Cl:14])=[CH:10][CH:9]=2)[N:6]=1.C([Sn](CCCC)(CCCC)[C:25]1[CH2:26][CH2:27][O:28][CH2:29][CH:30]=1)CCC.[Cl-].[Li+].O1CCOCC1>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.[Cu]I>[CH2:18]([O:17][C:15]([C:4]1[S:3][C:2]([C:25]2[CH2:30][CH2:29][O:28][CH2:27][CH:26]=2)=[N:6][C:5]=1[CH2:7][C:8]1[CH:13]=[CH:12][C:11]([Cl:14])=[CH:10][CH:9]=1)=[O:16])[CH3:19]

Participants

7

Reactant 4

HCID 312751,4-DioxaneHCID 433294Lithium ChlorideHCID 222522584-Tributylstannyl-3,6-dihydro-2H-pyranHCID 66747997HCID 66747997, compound

Product 1

HCID 66749676HCID 66749676, compoundYield 38.9%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalyst

Procedure

A mixture of ethyl 2-bromo-4-(4-chlorobenzyl)-1,3-thiazole-5-carboxylate (289 mg, 0.802 mmol), tributyl(3,6-dihydro-2H-pyran-4-yl)stannane (332 mg, 0.890 mmol), tetrakis(triphenylphosphine)palladium(0) (46.4 mg, 0.0401 mmol), lithium chloride (1.20E2 mg, 2.82 mmol) and copper(I) iodide (45.8 mg, 0.241 mmol) in dry 1,4-dioxane (6.26 mL, 80.2 mmol) was degassed by vacuum and backfilling with argon four times, and then heated under argon at reflux for 3 hours. The mixture was filtered thru Celite, washing with 10% MeOH in DCM. Volatiles were removed in vacuo, and the residue was adsorbed to silica gel by concentrating a DCM solution to which silica gel had been added. Column chromatography (gradient elution, 0 to 20% EA in hexanes) afforded ethyl-4-(4-chlorobenzyl)-2-(3,6-dihydro-2H-pyran-4-yl)-1,3-thiazole-5-carboxylate (113 mg, 38.9%) as a white solid. 1H NMR (300 MHz, DMSO) δ 7.35-7.31 (m, 2H), 7.27-7.23 (m, 2H), 6.86-6.83 (m, 1H), 4.40 (s, 2H), 4.29 (q, J=6.9, 2H), 4.25-4.22 (m, 2H), 3.78 (t, J=5.4, 2H), 2.51-2.46 (m, 2H), 1.27 (t, J=6.9 Hz, 3H).

Workup

  1. customwas degassed by vacuum and backfilling with argon four times
  2. temperatureheated under argon
  3. temperatureat reflux for 3 hours
  4. filtrationThe mixture was filtered thru Celite
  5. washwashing with 10% MeOH in DCM
  6. customVolatiles were removed in vacuo
  7. concentrationby concentrating a DCM solution to which silica gel
  8. additionhad been added
  9. washColumn chromatography (gradient elution, 0 to 20% EA in hexanes)

Sources & evidence

ORD record
ord-2fd29ab7bdf346c8b687e131e40922bd
Source dataset
uspto-grants-2014_08
Patent number
US08796271B2

Reaction notes

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