Lithium diisopropylamide → HCID 118098707, compound

HRID 708834Notes

Reaction equation

HRID 708834 reaction equation
[CH2:1]([O:8][C:9]([N:11]([CH2:13][C:14]1[CH:19]=[C:18]([N+:20]([O-:22])=[O:21])[CH:17]=[CH:16][C:15]=1[CH2:23][C:24]([O:26][CH2:27][CH3:28])=[O:25])[CH3:12])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Li+].CC([N-]C(C)C)C.FC(F)(F)S(O[CH2:43][CH:44]([F:46])[F:45])(=O)=O>C1COCC1>[CH2:1]([O:8][C:9]([N:11]([CH2:13][C:14]1[CH:19]=[C:18]([N+:20]([O-:22])=[O:21])[CH:17]=[CH:16][C:15]=1[CH:23]([CH2:43][CH:44]([F:46])[F:45])[C:24]([O:26][CH2:27][CH3:28])=[O:25])[CH3:12])=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 2724682Lithium diisopropylamideHCID 27740892,2-Difluoroethyl trifluoromethanesulfonateHCID 118098706HCID 118098706, compound

Product 1

HCID 118098707HCID 118098707, compoundYield 17.41%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a solution of 10B (345 mg, 0.893 mmol) in THF (5 mL) at −78° C., was added LDA (2 M, heptane, THF and ethylbenzene) (0.536 mL, 1.071 mmol). The red/black mixture was stirred at −78° C. for 20 min, then a solution of 2,2-difluoroethyl trifluoromethanesulfonate (210 mg, 0.982 mmol) in THF (0.5 mL) was added dropwise. The reaction was removed from the cooling bath and was stirred at rt for 4 h. The reaction mixture was quenched with sat. NH4Cl, diluted with EtOAc. The organic phase was washed with H2O and brine, dried (Na2SO4) and concentrated. The crude product was purified by flash chromatography (loaded in chloroform onto a 12 g column and eluted with a gradient from 0 to 50% ethyl acetate/hexanes) to give 10C (70 mg, 0.155 mmol, 17.41% yield) pale yellow oil. MS (ESI) m/z: 450.9 (M+H)+. 1H NMR (400 MHz, chloroform-d) δ ppm 8.15 (d, J=7.91 Hz, 1H) 7.97-8.11 (m, 1H) 7.50 (d, J=7.47 Hz, 1H) 7.24-7.43 (m, 5H) 5.10-5.29 (m, 2H) 4.57-4.87 (m, 2H) 4.00-4.39 (m, 3H) 2.91 (br. s., 3H) 2.57-2.87 (m, 1H) 2.19 (s, 1H) 1.05-1.33 (m, 3H).

Workup

  1. customThe reaction was removed from the cooling bath
  2. stirringwas stirred at rt for 4 h
  3. customThe reaction mixture was quenched with sat. NH4Cl
  4. additiondiluted with EtOAc
  5. washThe organic phase was washed with H2O and brine
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated
  8. customThe crude product was purified by flash chromatography (
  9. washeluted with a gradient from 0 to 50% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-c17891d5830b496986dc61be71d7f79c
Source dataset
uspto-grants-2015_11
Patent number
US09174974B2

Reaction notes

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