Sodium hydride → 2-(3-Cyano-3-(3,4-dichlorophenyl)propyl)oxytetrahydropyran

HRID 2256022Notes

Reaction equation

HRID 2256022 reaction equation
[H-].[Na+].[Cl:3][C:4]1[CH:5]=[C:6]([CH2:11][C:12]#[N:13])[CH:7]=[CH:8][C:9]=1[Cl:10].[O:14]1[CH2:19][CH2:18][CH2:17][CH2:16][CH:15]1[O:20][CH2:21][CH2:22]Br>O1CCCC1.[Cl-].[NH4+]>[O:14]1[CH2:19][CH2:18][CH2:17][CH2:16][CH:15]1[O:20][CH2:21][CH2:22][CH:11]([C:6]1[CH:7]=[CH:8][C:9]([Cl:10])=[C:4]([Cl:3])[CH:5]=1)[C:12]#[N:13]

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 76690(3,4-Dichlorophenyl)acetonitrileHCID 866212-(2-Bromoethoxy)tetrahydro-2H-pyran

Product 1

HCID 156708072-(3-Cyano-3-(3,4-dichlorophenyl)propyl)oxytetrahydropyranYield 61.8%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 25517Ammonium ChlorideSolvent

Procedure

To a solution of sodium hydride (218.0 g of a 55% oil suspension) in tetrahydrofuran (4 L) at 10° C. in an ice/water bath was added 3,4-dichlorophenylacetonitrile (893.0 g) in tetrahydrofuran (2 L) over a period of 45 minutes, and the resulting solution was allowed to stir for 2 hours at room temperature. The mixture was cooled in an ice/water bath and 2-tetrahydropyran-2-yloxyethyl bromide (1076.0 g) was dropped in as a neat oil over a period of 25 minutes. The mixture was stirred overnight at room temperature and divided into four 2-liter portions. Each portion was diluted with saturated ammonium chloride (3 L) and extracted with ether (500 mL). The combined organic layers were washed (aqueous ammonium chloride), dried, and evaporated. The resulting material was chromatographed, with hexane:dichloromethane (gradient 100:0, 0:100) as eluent, to give the nitrile as an oil (932 g); NMR: 7.47 (m, 4), 7.20 (m, 2), 4.57 (m, 2), 4.08 (m, 2), 3.85 (m, 4), 3.54 (m, 3), 3.37 (m, 1), 2.15 (m, 4), 1.77 (m, 4), 1.56 (m, 8).

Workup

  1. temperatureThe mixture was cooled in an ice/water bath
  2. stirringThe mixture was stirred overnight at room temperature
  3. extractionextracted with ether (500 mL)
  4. washThe combined organic layers were washed (aqueous ammonium chloride)
  5. customdried
  6. customevaporated
  7. customThe resulting material was chromatographed, with hexane

Sources & evidence

ORD record
ord-c1f5a0eecc0746e3965b8c8d0eb9b274
Source dataset
uspto-grants-1997_08
Patent number
US05654299

Reaction notes

Loading…