Dimethyl Sulfate → 2-[Bis(cyclopropylmethyl)amino]-6-fluoropyridine-3-carbaldehyde

HRID 1911796Notes

Reaction equation

HRID 1911796 reaction equation
[OH-].[Na+].FC(F)(F)C1C=C(C=C(C(F)(F)F)C=1)CN([CH2:15][C:16]1[C:17]([N:23]([CH2:28][CH:29]2[CH2:31][CH2:30]2)[CH2:24][CH:25]2[CH2:27][CH2:26]2)=[N:18][C:19]([F:22])=[CH:20][CH:21]=1)C1NN=NN=1.S(OC)(OC)(=O)=[O:42]>O.ClCCl.[Br-].C([N+](CCCC)(CCCC)CCCC)CCC>[CH:25]1([CH2:24][N:23]([CH2:28][CH:29]2[CH2:31][CH2:30]2)[C:17]2[C:16]([CH:15]=[O:42])=[CH:21][CH:20]=[C:19]([F:22])[N:18]=2)[CH2:27][CH2:26]1

Participants

7

Reactant 3

HCID 6497Dimethyl SulfateHCID 14798Sodium HydroxideHCID 178505795HCID 178505795, compound

Product 1

HCID 587957962-[Bis(cyclopropylmethyl)amino]-6-fluoropyridine-3-carbaldehydeYield 125.5%

Reagents, catalysts & solvents 3

HCID 74236Tetrabutylammonium BromideCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To sodium hydroxide (33.6 mg, 0.8 mmol) stirred in water (2 mL) was added (3-{[(3,5-bis-trifluoromethyl-benzyl)-(1H-tetrazol-5-yl)-amino]-methyl}-6-fluoro-pyridine-2-yl)-bis-cyclopropylmethyl-amine (222 mg, 0.4 mmol) in dichloromethane (5 mL). After stirring for 15 minutes, dimethyl sulfate (0.05 mL, 0.44 mmol) and tetrabutylammonium bromide (7.5 mg, 0.0176 mmol) was added and the solution was left to stir at room temperature for 1 hour. The solution was extracted with dichloromethane (2×15 mL). The combined organic layers were washed with water and brine, dried over sodium sulfate, filtered and then concentrated under vacuum to give an orange oily product. Purification by silica gel chromatography and eluting with 30% ethyl acetate in hexanes afforded the title compound as an orange oil (124.6 mg, yield: 56%).

Workup

  1. waitthe solution was left
  2. stirringto stir at room temperature for 1 hour
  3. extractionThe solution was extracted with dichloromethane (2×15 mL)
  4. washThe combined organic layers were washed with water and brine
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under vacuum
  8. customto give an orange oily product
  9. customPurification by silica gel chromatography
  10. washeluting with 30% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-3e4758b1b8b84e1583ec88404d498996
Source dataset
uspto-grants-2013_12
Patent number
US08604055B2

Reaction notes

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