Formaldehyde → 2-Bromo-5-[(1-methyl-3-azetidinyl)oxy]pyridine

HRID 2069727Notes

Reaction equation

HRID 2069727 reaction equation
F[C:2](F)(F)C(O)=O.[NH:8]1[CH2:11][CH:10]([O:12][C:13]2[CH:14]=[CH:15][C:16]([Br:19])=[N:17][CH:18]=2)[CH2:9]1.C=O.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>ClCCl>[Br:19][C:16]1[CH:15]=[CH:14][C:13]([O:12][CH:10]2[CH2:11][N:8]([CH3:2])[CH2:9]2)=[CH:18][N:17]=1

Participants

5

Reactant 3

HCID 712FormaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 866450865-(Azetidin-3-yloxy)-2-bromo-pyridine trifluoro-acetic acid salt

Product 1

HCID 594737702-Bromo-5-[(1-methyl-3-azetidinyl)oxy]pyridineYield 104.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

In a solution of 5-(Azetidin-3-yloxy)-2-bromo-pyridine trifluoro-acetic acid salt (0.5 g, 1.46 mmol) in dichloromethane (20 mL), add formaldehyde aqueous solution (37%, 0.58 mL, 7.29 mmol). Then add Na(OAc)3BH (0.774 g, 3.65 mmo) carefully. The reaction was stirred at room temperature under argon for 45 min. The reaction was quenched with water (30 mL), and then extracted with dichloromethane (3×20 mL). The combined organic phase was washed thoroughly with brine and water. Evaporation of solvent afford 2-Bromo-5-(1-methyl-azetidin-3-yloxy)-pyridine (0.37 g, yield 98%), which was pure enough for next step.

Workup

  1. customThe reaction was quenched with water (30 mL)
  2. extractionextracted with dichloromethane (3×20 mL)
  3. washThe combined organic phase was washed thoroughly with brine and water
  4. customEvaporation of solvent

Sources & evidence

ORD record
ord-9cca5c8ee4d745c3841362a2ae59b7ac
Source dataset
uspto-grants-2012_10
Patent number
US08299077B2

Reaction notes

Loading…