Epichlorohydrin → (1R)-2-Hydroxymethyl-1-(1-naphthyl)-cyclopropanecarbonitrile

HRID 1096746Notes

Reaction equation

HRID 1096746 reaction equation
[C:1]1([CH2:11][C:12]#[N:13])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1.C[Si]([NH-])(C)C.C[Si]([NH-])(C)C.[Na+].[Na+].[CH2:26]([CH:28]1[O:30][CH2:29]1)Cl.C(OCC)(=O)C.CCCCCC>O1CCCC1>[OH:30][CH2:29][CH:28]1[CH2:26][C@@:11]1([C:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1)[C:12]#[N:13]

Participants

6

Reactant 4

HCID 7835EpichlorohydrinHCID 85961-NaphthaleneacetonitrileHCID 21226206Ethyl acetate hexaneHCID 86599718Sodiumbis(trimethylsilylamide)2×

Product 1

HCID 66781211(1R)-2-Hydroxymethyl-1-(1-naphthyl)-cyclopropanecarbonitrileYield 69.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent4×

Conditions

Temperature
-15 °C

Procedure

1-Naphthylacetonitrile (30 g, 180 mmole) was dissolved in dry tetrahydrofuran (THF, 300 mL) under nitrogen atmosphere, cooled to −15° C. and sodium-bis (trimethylsilylamide) in 1M tetrahydrofuran (180 mL) was added drop wise at −15° C. The resulting brown mixture was stirred for 45 min at −10° C. to 0° C. Then cooled the reaction mass to −15° C. A solution of S-(+) epichlorohydrin (16.6 g, 180 mmol) in tetrahydrofuran (20 mL) was added drop wise at −15° C. and stirred for 30 minutes. Sodiumbis (trimethylsilylamide) in 1M THF (180 mL) is added drop wise at −15° C. and the mixture was stirred for 45 min. The temperature of the reaction mass was then gradually raised to room temperature and maintained at room temperature for 30 minutes. The reaction is monitored by TLC (ethyl acetate/hexane (1:1)). The reaction was quenched with water (80mL). The aqueous layer was extracted with ethyl acetate (2×75 mL).The combined organic layer was washed with brine solution (200 mL), dried over anhydrous sodium sulphate, filtered and evaporated under reduced pressure to yield 55 g of crude oil, which was purified by column chromatography (silica gel, ethyl acetate/hexane (10:90) to yield 28 g (69%) of product. The 1H NMR shows mixture of diasteromers (2:1 cis/trans). 1H NMR δ((300 MHz,CDCl3, partial assignment): 1.57-1.62 (2H,m), 1.92-2.03 (1H,m), 3.10-3.25 (1H,br,s), 3.91-3.97 (1H,m) 4.22-4.27 (1H,m), 7.37-7.69 (4H,m), 7.82-7.92 (2H,m), 8.36-8.49 (1H,m).

Workup

  1. temperatureThen cooled the reaction mass to −15° C
  2. stirringstirred for 30 minutes
  3. stirringthe mixture was stirred for 45 min
  4. temperatureThe temperature of the reaction mass was then gradually raised to room temperature
  5. temperaturemaintained at room temperature for 30 minutes
  6. customThe reaction was quenched with water (80mL)
  7. extractionThe aqueous layer was extracted with ethyl acetate (2×75 mL).The combined organic layer
  8. washwas washed with brine solution (200 mL)
  9. dry with materialdried over anhydrous sodium sulphate
  10. filtrationfiltered
  11. customevaporated under reduced pressure
  12. customto yield 55 g of crude oil, which
  13. customwas purified by column chromatography (silica gel, ethyl acetate/hexane (10:90)

Sources & evidence

ORD record
ord-560194bb314f4f85b25340d99de03a94
Source dataset
uspto-grants-2012_03
Patent number
US08138377B2

Reaction notes

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