Cyclopropylacetonitrile → (S)-N-{3-[4-(4-(1-Cyclopropyl-1-cyanomethyl)-4-hydroxypiperidin-1-yl)-3-fluorophenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide

HRID 1026674Notes

Reaction equation

HRID 1026674 reaction equation
[CH:1]1([CH2:4][C:5]#[N:6])[CH2:3][CH2:2]1.[Li]CCCC.[O:12]=[C:13]1[CH2:18][CH2:17][N:16]([C:19]2[CH:24]=[CH:23][C:22]([N:25]3[CH2:29][C@H:28]([CH2:30][NH:31][C:32](=[O:34])[CH3:33])[O:27][C:26]3=[O:35])=[CH:21][C:20]=2[F:36])[CH2:15][CH2:14]1>O1CCCC1>[CH:1]1([CH:4]([C:13]2([OH:12])[CH2:14][CH2:15][N:16]([C:19]3[CH:24]=[CH:23][C:22]([N:25]4[CH2:29][C@H:28]([CH2:30][NH:31][C:32](=[O:34])[CH3:33])[O:27][C:26]4=[O:35])=[CH:21][C:20]=3[F:36])[CH2:17][CH2:18]2)[C:5]#[N:6])[CH2:3][CH2:2]1

Participants

5

Reactant 3

HCID 643447CyclopropylacetonitrileHCID 54375226N-[(5S)-3-[3-fluoro-4-(4-oxopiperidinyl)phenyl]-2-oxo-5-oxazolidinyl]methylacetamideHCID 178418339Butyllithium

Product 1

HCID 11339414(S)-N-{3-[4-(4-(1-Cyclopropyl-1-cyanomethyl)-4-hydroxypiperidin-1-yl)-3-fluorophenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamideYield 64%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of cyclopropyl acetonitrile (28 mmol) and was treated with n-BuLi (28 mmol) at −78° C. in tetrahydrofuran and was stirred for 1 hour. Addition of (S)—N-{3-[4-(4-oxo-piperidin-1-yl)-3-fluorophenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide (14.32 mmol) was done to the reaction mixture and stirred overnight. The reaction mixture was quenched with saturated ammonium chloride solution and was extracted with ethyl acetate. The organic layer was concentrated, dried and evaporated to afford a residue which was purified on silica gel column chromatography to provide title compound in 64% yield. M.P. 170-72° C. and MS (M+1)=431 (H+, 100%) for M.F.=C22H27FN4O4.

Workup

  1. stirringstirred overnight
  2. customThe reaction mixture was quenched with saturated ammonium chloride solution
  3. extractionwas extracted with ethyl acetate
  4. concentrationThe organic layer was concentrated
  5. customdried
  6. customevaporated
  7. customto afford a residue which
  8. customwas purified on silica gel column chromatography

Sources & evidence

ORD record
ord-f3fe60256881441f9cc6dab63acfdcd3
Source dataset
uspto-grants-2014_05
Patent number
US08729269B2

Reaction notes

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