Diethylamine → HCID 16103033, compound

HRID 1786301Notes

Reaction equation

HRID 1786301 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([CH2:8][CH2:9][CH2:10][CH2:11]O)[CH:5]=[C:4]([F:13])[C:3]=1[CH:14]([C:18]([O-:20])=[O:19])[C:15]([O-:17])=[O:16].C([N:23]([CH2:26]C)[CH2:24]C)C.CS(Cl)(=O)=O.[CH2:33](NCC)[CH3:34].O1CC[CH2:40][CH2:39]1>C(Cl)Cl>[CH3:26][N:23]([CH3:24])[CH2:11][CH2:10][CH2:9][CH2:8][C:6]1[CH:7]=[C:2]([F:1])[C:3]([CH:14]([C:18]([O:20][CH2:39][CH3:40])=[O:19])[C:15]([O:17][CH2:33][CH3:34])=[O:16])=[C:4]([F:13])[CH:5]=1

Participants

7

Reactant 5

HCID 8021DiethylamineHCID 8028TetrahydrofuranHCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 86597650HCID 86597650, compound

Product 1

HCID 16103033HCID 16103033, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 2-[2,6-difluoro-4-(4-hydroxybutyl)phenyl]malonate (2.0 g, 5.8 mmol) and triethylamine (2.43 mL, 17.4 mmol) in 15 ml of methylene chloride at 0° C. is added methanesulfonyl chloride (0.898 mL, 11.6 mmol). The resulting mixture is allowed to warm to room temperature in 1.5 h. The mixture is washed with 10% hydrochloric acid, saturated sodium bicarbonate, and saturated sodium chloride. The organic layer is dried over magnesium sulfate and concentrated to a yellow oil. The yellow oil thus obtained is stirred with 2.0 M diethylamine in tetrahydrofuran (56 mL, 112 mmol) at room temperature for 16 h, followed by concentration. The residue is diluted with ethyl acetate. The organic layer is washed with water and saturated sodium chloride, dried over magnesium sulfate, and concentrated to a residue. The residue is chromatographed over silica gel, eluting with a gradient of 100% ethyl acetate to 50% methyl alcohol in ethyl acetate to 100% methyl alcohol. Concentration provides diethyl 2-{4-[4-(dimethylamino)butyl]-2,6-difluorophenyl}malonate as a yellow oil (1.2 g). MS: m/z 372.2 (M+H).

Workup

  1. washThe mixture is washed with 10% hydrochloric acid, saturated sodium bicarbonate, and saturated sodium chloride
  2. dry with materialThe organic layer is dried over magnesium sulfate
  3. concentrationconcentrated to a yellow oil
  4. customThe yellow oil thus obtained
  5. concentrationfollowed by concentration
  6. additionThe residue is diluted with ethyl acetate
  7. washThe organic layer is washed with water and saturated sodium chloride
  8. dry with materialdried over magnesium sulfate
  9. concentrationconcentrated to a residue
  10. customThe residue is chromatographed over silica gel
  11. washeluting with a gradient of 100% ethyl acetate to 50% methyl alcohol in ethyl acetate to 100% methyl alcohol
  12. concentrationConcentration

Sources & evidence

ORD record
ord-d092c670c40a423091b1f4ce5020007d
Source dataset
uspto-grants-2009_03
Patent number
US07507739B2

Reaction notes

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