Lithium Hydroxide → HCID 68284762, compound

HRID 2204224Notes

Reaction equation

HRID 2204224 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([C:8]([O:10]C)=[O:9])=[N:6][CH:7]=1.[SH-:12].[Na+].Br[CH2:15][CH:16]1[CH2:19][CH2:18][CH2:17]1.[Li+].[OH-:21].CN(C=[O:26])C>>[CH:16]1([CH2:15][S:12]([C:2]2[CH:3]=[CH:4][C:5]([C:8]([OH:10])=[O:9])=[N:6][CH:7]=2)(=[O:26])=[O:21])[CH2:19][CH2:18][CH2:17]1

Participants

6

Reactant 5

HCID 3939Lithium HydroxideHCID 6228DimethylformamideHCID 28015Sodium hydrosulfideHCID 2734658(Bromomethyl)cyclobutaneHCID 7016458Methyl 5-bromopyridine-2-carboxylate

Product 1

HCID 68284762HCID 68284762, compound

Conditions

Temperature
65 °C

Procedure

To a 100 mL round bottom flask was added methyl 5-bromopyridine-2-carboxylate (0.5 g, 2.3 mmol) followed by DMF (5 mL) and sodium sulfanide (259 mg, 4.6 mmol). The reaction was heated at 65° C. overnight. Bromomethylcyclobutane (260 μL, 2.3 mmol) was added and the reaction was allowed to stir for 30 minutes while cooling to 25° C. The reaction was then quenched with brine and extracted with ethyl acetate 3 times. The organic layers were combined and dried over sodium sulfate and the solvent was evaporated. The crude reaction mixture was then treated with 50 mL of Clorox® bleach and allowed to stir for 30 minutes. LiOH (5 mL of 3M) was added and the reaction was allowed to stir for 1 h. The reaction was extracted with ethyl acetate and the organic layer was discarded. The aqueous layer was acidified to pH 2 and extracted with ethyl acetate 3 times. The organic layers were combined and dried over sodium sulfate. The crude product was purified via HPLC (1-99%) ACN:H2O with a 0.1% TFA modifier. 5-(Cyclobutylmethylsulfonyl)picolinic acid (39 mg) was isolated as a white solid. 1H NMR (400 MHz, MeOD) δ 9.11 (dd, J=2.2, 0.8 Hz, 1H), 8.47 (dd, J=8.2, 2.2 Hz, 1H), 8.35 (dd, J=8.2, 0.8 Hz, 1H), 3.47 (d, J=7.3 Hz, 2H), 2.80-2.66 (m, 1H), 2.11-2.00 (m, 2H), 1.97-1.75 (m, 4H).

Workup

  1. temperaturewhile cooling to 25° C
  2. customThe reaction was then quenched with brine
  3. extractionextracted with ethyl acetate 3 times
  4. dry with materialdried over sodium sulfate
  5. customthe solvent was evaporated
  6. customThe crude reaction mixture
  7. additionwas then treated with 50 mL of Clorox® bleach
  8. stirringto stir for 30 minutes
  9. stirringto stir for 1 h
  10. extractionThe reaction was extracted with ethyl acetate
  11. extractionextracted with ethyl acetate 3 times
  12. dry with materialdried over sodium sulfate
  13. customThe crude product was purified via HPLC (1-99%) ACN

Sources & evidence

ORD record
ord-dbd9e1dd7fb548a7b2f4bd10421a00f4
Source dataset
uspto-grants-2016_06
Patent number
US09365588B2

Reaction notes

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