Hydrochloric Acid → 5-Bromo-6-(3-methyl-oxetan-3-ylmethoxy)-pyridine-2-carboxylic acid

HRID 927722Notes

Reaction equation

HRID 927722 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]([C:9]([OH:11])=[O:10])=[N:6][C:7]=1Cl.[CH3:12][C:13]1([CH2:17][OH:18])[CH2:16][O:15][CH2:14]1.[H-].[Na+].Cl>CN(C=O)C.C(OCC)(=O)C>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([C:9]([OH:11])=[O:10])=[N:6][C:7]=1[O:18][CH2:17][C:13]1([CH3:12])[CH2:16][O:15][CH2:14]1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 1378373-Methyl-3-oxetanemethanolHCID 446077145-Bromo-6-chloropicolinic acid

Product 1

HCID 710878905-Bromo-6-(3-methyl-oxetan-3-ylmethoxy)-pyridine-2-carboxylic acidYield 27.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 5-bromo-6-chloropicolinic acid (Example 280a) (0.75 g, 3.17 mmol) in dry DMF (18 ml) under argon was added (3-methyloxetan-3-yl)-methanol (389 mg, 3.81 mmol) and NaH (279 mg, 6.98 mmol) was added by portions. The reaction mixture was stirred at room temperature for 20 min until gas release ceased. The reaction mixture was then stirred at 110° C. for 16 h. The reaction mixture was diluted with ethyl acetate, and the solution was poured into a separatory funnel with 10 ml aq. solution 1.0M HCl. After extraction, the organic phase was collected and the aqueous phase was back extracted with ethylacetate. The organic phases were combined, dried over Na2SO4 and evaporated down in vacuo. The residue was purified by preparative HPLC to give the title compound (260 mg, 27%), MS (EI): m/e=302.0 [M+H]+.

Workup

  1. additionwas added by portions
  2. stirringThe reaction mixture was then stirred at 110° C. for 16 h
  3. extractionAfter extraction
  4. customthe organic phase was collected
  5. extractionthe aqueous phase was back extracted with ethylacetate
  6. dry with materialdried over Na2SO4
  7. customevaporated down in vacuo
  8. customThe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-4ac2df4c0129417c99174e5f3ee655e9
Source dataset
uspto-grants-2016_03
Patent number
US09290451B2

Reaction notes

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