Chloroacetonitrile → HCID 89375784, compound

HRID 1752250Notes

Reaction equation

HRID 1752250 reaction equation
[CH3:1][O:2][C:3]1[CH:22]=[CH:21][C:6]([C:7]([CH:9]2[CH2:14][CH2:13][N:12]([C@H:15]3[CH2:19][CH2:18][NH:17][C:16]3=[O:20])[CH2:11][CH2:10]2)=[O:8])=[CH:5][C:4]=1[CH3:23].Br[CH2:25][C:26]#[N:27].[H-].[Na+].ClCC#N>C1COCC1>[CH3:1][O:2][C:3]1[CH:22]=[CH:21][C:6]([C:7]([CH:9]2[CH2:14][CH2:13][N:12]([C@H:15]3[CH2:19][CH2:18][N:17]([CH2:25][C:26]#[N:27])[C:16]3=[O:20])[CH2:11][CH2:10]2)=[O:8])=[CH:5][C:4]=1[CH3:23]

Participants

6

Reactant 4

HCID 7856ChloroacetonitrileHCID 11534BromoacetonitrileHCID 24758Sodium hydrideHCID 71212238HCID 71212238, compound

Product 1

HCID 89375784HCID 89375784, compoundYield 71.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (S)-3-[4-(4-methoxy-3-methyl-benzoyl)-piperidin-1-yl]-pyrrolidin-2-one (6.32 mmol, 2.0 g) and bromoacetonitrile (18.96 mmol, 2.275 g) in THF (60 mL) at 0° C. was added sodium hydride (60%, 18.96 mmol, 0.76 g) and allowed to stir under N2 for 1 hour. Allowed to warm to ambient temperature and chloroacetonitrile (2 mL) was added. After 30 min the reaction was cooled to 0° C. and quenched with saturated ammonium chloride solution. Flash column chromatography (silica) was performed eluting with 3% MeOH/ethyl acetate to 15% MeOH/ethyl acetate and provided the title compound as an red-brown foam (1.6 g, 71.2% yield). Calculated molecular formula=C20H25N3O3=355.4406. found MS (ESI) m/e 356.6 (M+H+); analytical RP-HPLC (Novapak 150×3.9 mm C18 column: mobile phase: 10-90% acetonitrile/water with 0.1% TFA, at 2 mL/min over 5 min.) retention time=2.831 min.

Workup

  1. temperatureAfter 30 min the reaction was cooled to 0° C.
  2. customquenched with saturated ammonium chloride solution
  3. washFlash column chromatography (silica) was performed eluting with 3% MeOH/ethyl acetate to 15% MeOH/ethyl acetate

Sources & evidence

ORD record
ord-c41660da35bc4c9a86a0359e373dd1d7
Source dataset
uspto-grants-2015_10
Patent number
US09163003B2

Reaction notes

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