Tetrahydrofuran → HCID 178462429, compound

HRID 1766938Notes

Reaction equation

HRID 1766938 reaction equation
[H-].[K+].O1CCCC1.[F:8][C:9]1[CH:14]=[C:13]([F:15])[CH:12]=[CH:11][C:10]=1[C@@:16]([OH:45])([CH2:39][N:40]1[CH:44]=[N:43][CH:42]=[N:41]1)[C@H:17]([S:19][C@@H:20]1[CH2:25][O:24][C@@H:23](/[CH:26]=[CH:27]/[CH:28]=[CH:29]/[C:30]2[CH:37]=[CH:36][C:33]([C:34]#[N:35])=[CH:32][C:31]=2[F:38])[O:22][CH2:21]1)[CH3:18].Cl[C:47]([O:49][CH2:50][CH2:51][Cl:52])=[O:48]>CCCCCC.C(OCC)(=O)C>[C:47](=[O:48])([O:45][C@:16]([C:10]1[CH:11]=[CH:12][C:13]([F:15])=[CH:14][C:9]=1[F:8])([CH2:39][N:40]1[CH:44]=[N:43][CH:42]=[N:41]1)[C@H:17]([S:19][C@@H:20]1[CH2:25][O:24][C@@H:23](/[CH:26]=[CH:27]/[CH:28]=[CH:29]/[C:30]2[CH:37]=[CH:36][C:33]([C:34]#[N:35])=[CH:32][C:31]=2[F:38])[O:22][CH2:21]1)[CH3:18])[O:49][CH2:50][CH2:51][Cl:52]

Participants

7

Reactant 4

HCID 8028Tetrahydrofuran2×HCID 123052-Chloroethyl chloroformateHCID 82127Potassium hydrideHCID 178462432HCID 178462432, compound

Product 1

HCID 178462429HCID 178462429, compoundYield 88.8%

Reagents, catalysts & solvents 2

HCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

A mixture of potassium hydride (30% dispersion in mineral oil; 739 mg, 5.53 mmol) and tetrahydrofuran (8 ml) was cooled to 0° C., and 4-[(1E,3E)-4-[trans-5-[[(1R,2R)-2-(2,4-difluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazol-1-yl)propyl]thio]-1,3-dioxan-2-yl]-1,3-butadienyl]-3-fluorobenzonitrile (1.00 g, 1.84 mmol) described in Reference example 1 was added thereto with stirring, then the mixture was stirred at room temperature for 30 minutes. The mixture was cooled to 0° C., and then a mixture of 2-chloroethyl chloroformate (315 mg, 2.21 mmol) and tetrahydrofuran (1.5 ml) was added thereto with stirring. The resulting mixture was stirred at room temperature for 18 hours. After cooling, the mixture was partitioned between ethyl acetate and water, and the organic layer was washed successively with water and a saturated aqueous solution of sodium chloride, and the solvent was distilled off under reduced pressure to give an oily residue. The residue was subjected to column chromatography (eluent; ethyl acetate:hexane=1:1) to afford the title compound (1.06 g, 88% yield) as a colorless oil.

Workup

  1. additionwas added
  2. stirringthe mixture was stirred at room temperature for 30 minutes
  3. temperatureThe mixture was cooled to 0° C.
  4. additionwas added
  5. stirringwith stirring
  6. stirringThe resulting mixture was stirred at room temperature for 18 hours
  7. temperatureAfter cooling
  8. customthe mixture was partitioned between ethyl acetate and water
  9. washthe organic layer was washed successively with water
  10. distillationa saturated aqueous solution of sodium chloride, and the solvent was distilled off under reduced pressure
  11. customto give an oily residue

Sources & evidence

ORD record
ord-f8137b37bee04ab4b52d9d7b6536bb91
Source dataset
uspto-grants-2007_06
Patent number
US07230023B2

Reaction notes

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