Tetrahydrofuran → HCID 59135248, compound

HRID 1994648Notes

Reaction equation

HRID 1994648 reaction equation
[F:1][C:2]1[C:7]([CH:8]([CH3:10])[CH3:9])=[CH:6][C:5]([C:11]2[CH:16]=[CH:15][C:14]([C:17]([F:20])([F:19])[F:18])=[CH:13][C:12]=2[CH:21]([NH:24][CH2:25][C:26]2[CH:31]=[CH:30][C:29]([O:32][CH3:33])=[CH:28][CH:27]=2)[C:22]#[N:23])=[C:4]([O:34][CH3:35])[CH:3]=1.[H-].[H-].[H-].[H-].[Li+].[Al+3].C1C[O:45][CH2:44]C1>CCOCC>[F:1][C:2]1[C:7]([CH:8]([CH3:10])[CH3:9])=[CH:6][C:5]([C:11]2[CH:16]=[CH:15][C:14]([C:17]([F:20])([F:19])[F:18])=[CH:13][C:12]=2[CH:21]2[N:24]([CH2:25][C:26]3[CH:27]=[CH:28][C:29]([O:32][CH3:33])=[CH:30][CH:31]=3)[C:44](=[O:45])[NH:23][CH2:22]2)=[C:4]([O:34][CH3:35])[CH:3]=1

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 21226445Aluminium lithium hydrideHCID 66717175HCID 66717175, compound

Product 1

HCID 59135248HCID 59135248, compound

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Procedure

To a 0° C. solution of 100 mg of [4′-fluoro-5′-isopropyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-yl][(4-methoxybenzyl)amino]acetonitrile in 4 mL of THF was added 620 μL of a 1 M solution of LiAlH4 in Et2O. The cooling bath was removed and the mixture was stirred for 45 min at r.t. The mixture was recooled to 0° C. and carefully quenched by dropwise addition of 24 μL of water, 24 μL of 15% aqueous NaOH solution, and 60 μL of water. The solids were filtered, washing liberally with Et2O, and the filtrate was concentrated. The residue was dissolved in 2 mL of CH2Cl2 and cooled to 0° C. Triethylamine (55 μL) and then triphosgene (32 mg) were added. The mixture was stirred for 45 min at 0° C. The reaction mixture was partitioned between 10 mL of EtOAc and 10 mL of water. The aqueous was extracted with 10 mL of EtOAc and the combined organics were washed with 10 mL of brine, dried (Na2SO4), and concentrated. The residue was purified by flash chromatography on a Biotage Horizon, 25S column, eluting with 1 CV of 15% EtOAc in hexanes followed by a linear gradient of 15→100% EtOAc in hexanes over 10 CV to provide the title compound. Mass spectrum (ESI) 517.3 (M+1).

Workup

  1. customThe cooling bath was removed
  2. customwas recooled to 0° C.
  3. customcarefully quenched by dropwise addition of 24 μL of water, 24 μL of 15% aqueous NaOH solution, and 60 μL of water
  4. filtrationThe solids were filtered
  5. washwashing liberally with Et2O
  6. concentrationthe filtrate was concentrated
  7. dissolutionThe residue was dissolved in 2 mL of CH2Cl2
  8. temperaturecooled to 0° C
  9. additionTriethylamine (55 μL) and then triphosgene (32 mg) were added
  10. stirringThe mixture was stirred for 45 min at 0° C
  11. customThe reaction mixture was partitioned between 10 mL of EtOAc and 10 mL of water
  12. extractionThe aqueous was extracted with 10 mL of EtOAc
  13. washthe combined organics were washed with 10 mL of brine
  14. dry with materialdried (Na2SO4)
  15. concentrationconcentrated
  16. customThe residue was purified by flash chromatography on a Biotage Horizon, 25S column
  17. washeluting with 1 CV of 15% EtOAc in hexanes

Sources & evidence

ORD record
ord-7426a4f89e574bd4a07a3d0e99e39d1f
Source dataset
uspto-grants-2010_01
Patent number
US07652049B2

Reaction notes

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