Bromoacetonitrile → HCID 67354460, compound

HRID 1670830Notes

Reaction equation

HRID 1670830 reaction equation
[CH3:1][O:2][C:3](=[O:13])[CH2:4][N:5]1[CH2:10][CH2:9][C:8]([F:12])([F:11])[CH2:7][CH2:6]1.[CH:14]([N-:17]C(C)C)(C)[CH3:15].[Li+].CCCCCCC.C1COCC1.C(C1C=CC=CC=1)C.BrCC#N.[NH4+].[Cl-]>C1COCC1.C(OCC)(=O)C>[CH3:1][O:2][C:3](=[O:13])[CH:4]([N:5]1[CH2:6][CH2:7][C:8]([F:11])([F:12])[CH2:9][CH2:10]1)[CH2:15][C:14]#[N:17]

Participants

8

Reactant 5

HCID 11534BromoacetonitrileHCID 25517Ammonium ChlorideHCID 2724682Lithium diisopropylamideHCID 22742125Tetrahydrofuran heptane ethylbenzolHCID 67047003HCID 67047003, compound

Product 1

HCID 67354460HCID 67354460, compoundYield 22%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-78 °C

Procedure

Treat a −78° C. solution of (4,4-difluoro-piperidin-1-yl)-acetic acid methyl ester (14.21 g, 73.6 mmol) (Preparation 33) in THF (150 mL) with a 2M solution of lithium diisopropylamide in heptane/THF/ethylbenzene (44.2 mL, 88.4 mmol) and stir at −78° C. for 20 minutes under N2. Treat the reaction with bromoacetonitrile (13.25 g, 110.5 mmol) and stir at −78° C. for 15 minutes. Warm the reaction to room temperature and stir 4 hours. Pour the reaction into saturated NH4Cl. Dilute the reaction with ethyl acetate and wash with water. Dry the organic layer with Na2SO4 and remove the solvent in vacuo to afford crude product. Then, purify on silica with a 0 to 100% ethyl acetate in hexanes gradient to afford 3.74 g (22%) of the titled product. Rf=0.50 (1/1 hexanes/ethyl acetate). ES MS (m/z): 233 (M+).

Workup

  1. additionTreat
  2. stirringstir at −78° C. for 15 minutes
  3. temperatureWarm
  4. customthe reaction to room temperature
  5. stirringstir 4 hours
  6. additionPour
  7. additionDilute
  8. washwash with water
  9. dry with materialDry the organic layer with Na2SO4
  10. customremove the solvent in vacuo
  11. customto afford crude product
  12. customThen, purify on silica with a 0 to 100% ethyl acetate in hexanes gradient

Sources & evidence

ORD record
ord-b5504ed458b24b3e9e37c1806e737c45
Source dataset
uspto-grants-2011_08
Patent number
US07994176B2

Reaction notes

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