Dimethylformamide → HCID 67076833, compound

HRID 899435Notes

Reaction equation

HRID 899435 reaction equation
[F:1][C:2]1([F:31])[CH2:30][CH:5]2[CH:6]([C:20]3[CH:25]=[CH:24][C:23]([O:26][CH2:27][O:28][CH3:29])=[CH:22][CH:21]=3)[O:7][C:8]3[C:13]([CH:4]2[CH2:3]1)=[CH:12][C:11]([O:14][CH2:15][O:16][CH3:17])=[CH:10][C:9]=3[C:18]#N.C[Li].C([Li])CCC.CN(C=[O:43])C.[BH4-].[Na+]>C1COCC1.CCOCC.CCOC(C)=O>[F:1][C:2]1([F:31])[CH2:30][CH:5]2[CH:6]([C:20]3[CH:25]=[CH:24][C:23]([O:26][CH2:27][O:28][CH3:29])=[CH:22][CH:21]=3)[O:7][C:8]3[C:9]([CH2:18][OH:43])=[CH:10][C:11]([O:14][CH2:15][O:16][CH3:17])=[CH:12][C:13]=3[CH:4]2[CH2:3]1

Participants

9

Reactant 5

HCID 6228DimethylformamideHCID 4311764Sodium borohydrideHCID 67076946HCID 67076946, compoundHCID 178418339ButyllithiumHCID 178418348HCID 178418348, compound

Product 1

HCID 67076833HCID 67076833, compound

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of preparation 16 (97 mg, 0.20 mmol) in 2 mL of THF at −78° C. add methyl lithium (0.062 mL of a 1.6 M solution in Et2O, 0.10 mmol) followed by n-butyllithium (0.25 mL of a 1.6 M solution in hexanes, 0.40 mmol). Stir the solution for 15 min and then add DMF (0.077 mL, 1.0 mmol). Stir the solution for 30 min and then quench the reaction with saturated aqueous ammonium chloride. Let the solution warm to room temperature, separate; and back extract the aqueous solution with EtOAc. Wash the combined organic solutions with ½ brine, brine, dry over Na2SO4, filter and concentrate. Dissolve the material in 1 mL of THF and 1 mL of methanol. Add sodium borohydride (35 mg, 0.93 mmol). Let the solution stir for 30 min and quench the reaction with saturated aqueous ammonium chloride. Dilute the solution with EtOAc, wash with brine, dry over Na2SO4, filter and concentrate. Adsorb the material to silica gel and purify by silica gel flash chromatography (10 g, 0-30% A/B, A=EtOAc, B=10% CH2Cl2 in hexanes) to afford 68 mg (0.16 mmol, 87%) of preparation 20. 1H NMR (400 MHz, CDCl3) δ 7.32-7.27 (m, 2H), 7.03-7.07 (m, 2H), 6.91 (d, 1H, J=2.6 Hz), 6.72 (d, 1H, J=2.6 Hz), 5.17 (s, 2H), 5.11 (d, 1H, J=10.5 Hz), 5.09 (d, 1H, J=10.1 Hz), 5.03 (bs, 1H), 4.73 (dd, 1H, J=6.6, 13.2 Hz), 4.68 (dd, 1H, J=6.6, 13.2 Hz), 3.66 (dt, 1H, J=3.5, 8.8 Hz), 3.47 (s, 3H), 3.46 (s, 3H), 2.86 (ddt, 1H, J=2.2, 10.1, 7.5 Hz), 2.72 (m, 1H), 2.31 (m, 1H), 2.18 (t, 1H, J=6.6 Hz), 2.13 (m, 1H), 1.86 (dt, 1H, J=7.5, 14.5 Hz).

Workup

  1. stirringStir the solution for 30 min
  2. customquench
  3. customthe reaction with saturated aqueous ammonium chloride
  4. customseparate
  5. extractionand back extract the aqueous solution with EtOAc
  6. washWash the combined organic solutions with ½ brine, brine
  7. dry with materialdry over Na2SO4
  8. filtrationfilter
  9. concentrationconcentrate
  10. dissolutionDissolve the material in 1 mL of THF
  11. stirringstir for 30 min
  12. customquench
  13. customthe reaction with saturated aqueous ammonium chloride
  14. washwash with brine
  15. dry with materialdry over Na2SO4
  16. filtrationfilter
  17. concentrationconcentrate
  18. custompurify by silica gel flash chromatography (10 g, 0-30% A/B
  19. customA=EtOAc, B=10% CH2Cl2 in hexanes) to afford
  20. custom68 mg (0.16 mmol, 87%) of preparation 20

Sources & evidence

ORD record
ord-7375ac73c48d41f99c725bbf01c4ddce
Source dataset
uspto-grants-2008_04
Patent number
US07354951B2

Reaction notes

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