Bromoacetonitrile → HCID 59468910, compound

HRID 1690101Notes

Reaction equation

HRID 1690101 reaction equation
[C:1]1([CH2:7][O:8][C:9]2[CH:10]=[C:11]([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:12]=[CH:13][CH:14]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C.Br[CH2:42][C:43]#[N:44]>C1COCC1>[C:43]([CH2:42][C@@:18]1([C:27]([O:29][CH3:30])=[O:28])[CH2:17][CH2:16][C@H:15]([C:11]2[CH:12]=[CH:13][CH:14]=[C:9]([O:8][CH2:7][C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)[CH:10]=2)[N:19]1[C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])#[N:44]

Participants

5

Reactant 3

HCID 11534BromoacetonitrileHCID 2733832Lithium HexamethyldisilazideHCID 59468945HCID 59468945, compound

Product 1

HCID 59468910HCID 59468910, compoundYield 54.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-30 °C

Procedure

To a solution of 1-(1,1-dimethylethyl) 2-methyl (2S,5R)-5-{3-[(phenylmethyl)oxy]phenyl}-1,2-pyrrolidinedicarboxylate (D43, 1.93 g, 4.7 mmol) in dry THF (20 mL) at −78° C. was added LiHMDS (5.2 mL of a 1M solution in THF, 5.2 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 bromoacetonitrile (2.2 mL, 30.9 mmol) was added. The reaction mixture was left under stirring for 1 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 (1.15 g, 54%); 1H NMR (400 MHz, CDCl3) δ(ppm): 2/1 mixture of rotamers; 7.31-7.47 (m, 5H); 7.22-7.28 (m, 2H); 7.07-7.12 (m, 1H); 6.85-6.91 (m, 1H); 5.05-5.17 (m, 3H major+3H minor); 4.94 (bs, 1H major); 3.88 (br. s, 3H); 3.79 (br. s, 1H minor); 3.52 (d, 1H major); 3.05-2.28 (m, 1H major+1H minor); 2.62-2.77 (m, 1H); 2.39-2.57 (m, 1H); 2.23-2.33 (m, 1H); 1.92-2.08 (m, 1H); 1.44 (s, 9H minor); 1.14 (s, 9H major).

Workup

  1. temperatureThen the yellow slurry was cooled to −78° C.
  2. waitThe reaction mixture was left
  3. stirringunder stirring for 1 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-7ea3baec95f545ebb48088bcb8b9e676
Source dataset
uspto-grants-2012_04
Patent number
US08153623B2

Reaction notes

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