Ammonium Chloride → 1-Tert-butyl 3-methyl 3-(5-chloropyridin-2-yl)azetidine-1,3-dicarboxylate

HRID 69527Notes

Reaction equation

HRID 69527 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5](F)=[N:6][CH:7]=1.[N:9]1([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:12][CH:11]([C:13]([O:15][CH3:16])=[O:14])[CH2:10]1.C[Si]([N-][Si](C)(C)C)(C)C.[K+].[NH4+].[Cl-]>C1(C)C=CC=CC=1>[CH3:16][O:15][C:13]([C:11]1([C:5]2[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][N:6]=2)[CH2:12][N:9]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:10]1)=[O:14]

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 3458175-Chloro-2-fluoropyridineHCID 3251421Potassium bis(trimethylsilyl)amideHCID 446076271-tert-Butyl 3-methyl azetidine-1,3-dicarboxylate

Product 1

HCID 866919031-Tert-butyl 3-methyl 3-(5-chloropyridin-2-yl)azetidine-1,3-dicarboxylate

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of 5-chloro-2-fluoropyridine (0.5 g, 3.8 mmol, Eq: 1.00) and 1-tert-butyl 3-methyl azetidine-1,3-dicarboxylate (818 mg, 3.8 mmol, Eq: 1.00) in toluene (5 ml) was added dropwise at 0° C. for 15 min a 0.5 M solution of KHMDS (7.6 ml, 3.8 mmol, Eq: 1.00) in toluene. The colorless solution turned into yellow-orange. After stirring at 0° C. for 45 min, the reaction mixture was allowed to warm to 20° C. and stirred for 2.5 h. A saturated aqueous NH4Cl solution (50 ml) was added and the aqueous phase was extracted with AcOEt (2×75 ml). The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated under reduced pressure. The crude material was purified by flash chromatography (silica gel, 12 g, 10% to 60% AcOEt in heptane) to yield a colorless gum (0.234 g; 19%). m/z=327.2 [M+H]+.

Workup

  1. temperatureto warm to 20° C.
  2. stirringstirred for 2.5 h
  3. extractionthe aqueous phase was extracted with AcOEt (2×75 ml)
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe crude material was purified by flash chromatography (silica gel, 12 g, 10% to 60% AcOEt in heptane)
  9. customto yield a colorless gum (0.234 g; 19%)

Sources & evidence

ORD record
ord-145d6c843df14c13afb62e1ae7984d5d
Source dataset
uspto-grants-2014_09
Patent number
US08822505B2

Reaction notes

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