2-Bromopropionitrile → HCID 59468941, compound

HRID 1690106Notes

Reaction equation

HRID 1690106 reaction equation
[C:1]1([CH2:7][O:8][C:9]2[CH:14]=[CH:13][C:12]([C@@H:15]3[N:19]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[C@H:18]([C:27]([O:29][CH3:30])=[O:28])[CH2:17][CH2:16]3)=[CH:11][CH:10]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C.Br[CH:42]([CH3:45])[C:43]#[N:44]>C1COCC1>[C:43]([CH2:42][CH2:45][C@@:18]1([C:27]([O:29][CH3:30])=[O:28])[CH2:17][CH2:16][C@H:15]([C:12]2[CH:11]=[CH:10][C:9]([O:8][CH2:7][C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)=[CH:14][CH:13]=2)[N:19]1[C:20]([O:22][C:23]([CH3:25])([CH3:26])[CH3:24])=[O:21])#[N:44]

Participants

5

Reactant 3

HCID 1405382-BromopropionitrileHCID 2733832Lithium HexamethyldisilazideHCID 59468944HCID 59468944, compound

Product 1

HCID 59468941HCID 59468941, compoundYield 52%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-30 °C

Procedure

To a solution of 1-(1,1-dimethylethyl) 2-methyl (2S,5R)-5-{4-[(phenylmethyl)oxy]phenyl}-1,2-pyrrolidinedicarboxylate (D6, 200 mg, 0.49 mmol) in dry THF (2 mL) at −78° C. was added LiHMDS (0.53 mL of a 1M solution in THF, 0.53 mmol). The mixture was allowed to warm to −30° C. and stirred for 30 min at this temperature. Then the yellow slurry was cooled to −78° C. and bromopropionitrile (0.24 mL, 2.92 mmol) was added. The reaction mixture was left under stirring for 2 h and then quenched with a saturated ammonium chloride solution. The aqueous layer was extracted with ethyl acetate, dried (Na2SO4), filtered and evaporated. The crude material was purified by chromatography on silica gel using cyclohexane/ethyl acetate (9:1) affording the title compound (107 mg, 52%).

Workup

  1. temperatureThen the yellow slurry was cooled to −78° C.
  2. waitThe reaction mixture was left
  3. stirringunder stirring for 2 h
  4. customquenched with a saturated ammonium chloride solution
  5. extractionThe aqueous layer was extracted with ethyl acetate
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. customevaporated
  9. customThe crude material was purified by chromatography on silica gel

Sources & evidence

ORD record
ord-29abbc3845c4450a9f2cb2a0cc1c725f
Source dataset
uspto-grants-2012_04
Patent number
US08153623B2

Reaction notes

Loading…