Bis(2-chloroethyl) ether → 4-(3-Chloro-4-fluorophenyl)-tetrahydro-pyran-4-carbonitrile

HRID 1868896Notes

Reaction equation

HRID 1868896 reaction equation
[H-].[Na+].Cl[CH2:4][CH2:5][O:6][CH2:7][CH2:8]Cl.[Cl:10][C:11]1[CH:12]=[C:13]([CH2:18][C:19]#[N:20])[CH:14]=[CH:15][C:16]=1[F:17]>CN1C(=O)CCC1.CCOCC>[Cl:10][C:11]1[CH:12]=[C:13]([C:18]2([C:19]#[N:20])[CH2:4][CH2:5][O:6][CH2:7][CH2:8]2)[CH:14]=[CH:15][C:16]=1[F:17]

Participants

6

Reactant 3

HCID 8115Bis(2-chloroethyl) etherHCID 24758Sodium hydrideHCID 27737253-Chloro-4-fluorobenzyl cyanide

Product 1

HCID 670994544-(3-Chloro-4-fluorophenyl)-tetrahydro-pyran-4-carbonitrile

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
0 °C

Procedure

NaH (60% in mineral oil, 14.3 g, 357 mmol) was suspended in NMP (143 mL) and cooled to 0° C. A solution of 1-chloro-2-(2-chloroethoxy)ethane (20.4 g, 143 mmol) and 3-chloro-4-fluorophenylacetonitrile (24.23 g, 143 mmol) in ether was then added dropwise via addition funnel. The resulting reaction mixture was stirred at 0° C. for 3 hours and then quenched with water, acidified with 5N HCl, diluted with 400 mL of diethyl ether, added to a separatory funnel, partitioned with water, washed 3 times with 100 mL of water, separated, dried over Na2SO4, and concentrated in vacuo to give the title (16.99 g) after flash chromatography. MS m/e=240 (M+H)+.

Workup

  1. customThe resulting reaction mixture
  2. customquenched with water
  3. additiondiluted with 400 mL of diethyl ether
  4. additionadded to a separatory funnel
  5. custompartitioned with water
  6. washwashed 3 times with 100 mL of water
  7. customseparated
  8. dry with materialdried over Na2SO4
  9. concentrationconcentrated in vacuo
  10. customto give the title (16.99 g) after flash chromatography

Sources & evidence

ORD record
ord-9afb6efc4bb94f58b60fc731d8f280c9
Source dataset
uspto-grants-2009_12
Patent number
US07635715B2

Reaction notes

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