Acetic Acid → HCID 71739075, compound

HRID 1025606Notes

Reaction equation

HRID 1025606 reaction equation
[Cl:1][C:2]1[N:7]=[CH:6][C:5]([O:8][C:9]([CH3:13])([CH3:12])[CH:10]=O)=[CH:4][CH:3]=1.C(=O)=O.C(#N)C.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[NH:38]1[CH2:41][CH2:40][CH2:39]1>ClCCl>[N:38]1([CH2:10][C:9]([CH3:13])([CH3:12])[O:8][C:5]2[CH:4]=[CH:3][C:2]([Cl:1])=[N:7][CH:6]=2)[CH2:41][CH2:40][CH2:39]1

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 10422AzetidineHCID 5049666Sodium triacetoxyborohydrideHCID 86587134Acetonitrile dry iceHCID 86662315HCID 86662315, compound2×

Product 1

HCID 71739075HCID 71739075, compoundYield 88%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

2-(6-Chloropyridin-3-yloxy)-2-methylpropanal [prepared according to US2012/40949 A1] (28 g, 140 mmol, Eq: 1.00) was taken up in dry dichloromethane (252 ml) and cooled to −10° C. (dry ice/acetonitrile cooling bath) under nitrogen atmosphere. Acetic acid (10.4 ml, 182 mmol) and sodium triacetoxyborohydride (41.6 g, 196 mmol) were added. Azetidine (17 ml, 252 mmol) was next added via drop-wise addition over 6 minutes, with efficient stirring. After complete addition the mixture was stirred for 5 minutes and then the cooling bath was removed and the material warmed to ambient. After 1 hour a saturated solution of aqueous sodium bicarbonate (200 ml) was added as well as dichloromethane (80 ml). The biphasic material was transferred to a separatory funnel, agitated and the organic phase was collected. This was shaken with a 5% solution of sodium bicarbonate (200 ml) and then a 50% diluted solution of brine (200 ml). The organic phase was collected and the aqueous phases were back extracted with methylene chloride (2 100 ml). The organic phase was combined, dried with magnesium sulfate, filtered and stripped. The crude remainder was purified via column chromatography (silica gel, 40 g) eluting with a 4% solution of methanol in dichloromethane to provide the desired 5-(2-azetidin-1-yl-1,1-dimethyl-ethoxy)-2-chloro-pyridin (29.66 g) as a golden brown mobile oil. LC/MS calc'd for C12H17ClN2O (m/e) 240.73, obs'd 241 (M+H, ES+).

Workup

  1. additionAfter complete addition the mixture
  2. customthe cooling bath was removed
  3. temperaturethe material warmed to ambient
  4. additionAfter 1 hour a saturated solution of aqueous sodium bicarbonate (200 ml) was added as well as dichloromethane (80 ml)
  5. customThe biphasic material was transferred to a separatory funnel
  6. stirringagitated
  7. customthe organic phase was collected
  8. stirringThis was shaken with a 5% solution of sodium bicarbonate (200 ml)
  9. customThe organic phase was collected
  10. extractionthe aqueous phases were back extracted with methylene chloride (2 100 ml)
  11. dry with materialdried with magnesium sulfate
  12. filtrationfiltered
  13. customThe crude remainder was purified via column chromatography (silica gel, 40 g)
  14. washeluting with a 4% solution of methanol in dichloromethane

Sources & evidence

ORD record
ord-53ba883e1f3947d6902bd6f6926eddc3
Source dataset
uspto-grants-2014_05
Patent number
US08729078B2

Reaction notes

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