Tert-butyl 4-(5-(methoxy(methyl)carbamoyl)pyridin-2-yl)piperazine-1-carboxylate → Tert-butyl 4-(5-(1-hydroxyethyl)pyridin-2-yl)piperazine-1-carboxylate

HRID 906075Notes

Reaction equation

HRID 906075 reaction equation
CON(C)[C:4]([C:6]1[CH:7]=[CH:8][C:9]([N:12]2[CH2:17][CH2:16][N:15]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:14][CH2:13]2)=[N:10][CH:11]=1)=[O:5].[CH3:26][Mg]Br>C1COCC1>[OH:5][CH:4]([C:6]1[CH:7]=[CH:8][C:9]([N:12]2[CH2:17][CH2:16][N:15]([C:18]([O:20][C:21]([CH3:23])([CH3:24])[CH3:22])=[O:19])[CH2:14][CH2:13]2)=[N:10][CH:11]=1)[CH3:26]

Participants

4

Reactant 2

HCID 86631940Tert-butyl 4-(5-(methoxy(methyl)carbamoyl)pyridin-2-yl)piperazine-1-carboxylateHCID 178418573HCID 178418573, compound

Product 1

HCID 67403230Tert-butyl 4-(5-(1-hydroxyethyl)pyridin-2-yl)piperazine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

tert-Butyl 4-(5-(methoxy(methyl)carbamoyl)pyridin-2-yl)piperazine-1-carboxylate (1.45 g, 4.1 mmol) was taken into THF (20 mL) and the solution cooled to 0° C. under a nitrogen atmosphere. Methyl magnesium bromide (3.0M in ethyl ether, 3.5 mL) was added in portions and the mixture was allowed to stir 10 minutes followed by addition of another 1.5 mL aliquot then the mixture was warmed to room temperature. The solution was then partitioned with ethyl ether and water and the organic phase washed with brine then dried over anhydrous sodium sulfate, filtered and concentrated. The residue was taken into methanol (25 mL) followed by portion-wise addition of sodium borohydride solid (250 mg) over 10 minutes. The mixture was allowed to stir at room temperature another 10 minutes then concentrated. The residue was partitioned with ethyl ether and water and the aqueous phase extracted ethyl ethyl ether (2×). The combined organic layers were dried over anhydrous sodium sulfate, filtered and concentrated to give tert-butyl 4-(5-(1-hydroxyethyl)pyridin-2-yl)piperazine-1-carboxylate (1.48 g) which was carried forward without further purification.

Workup

  1. additionfollowed by addition of another 1.5 mL aliquot
  2. temperaturethe mixture was warmed to room temperature
  3. customThe solution was then partitioned with ethyl ether and water
  4. washthe organic phase washed with brine
  5. dry with materialthen dried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. additionfollowed by portion-wise addition of sodium borohydride solid (250 mg) over 10 minutes
  9. stirringto stir at room temperature another 10 minutes
  10. concentrationthen concentrated
  11. customThe residue was partitioned with ethyl ether and water
  12. extractionthe aqueous phase extracted ethyl ethyl ether (2×)
  13. dry with materialThe combined organic layers were dried over anhydrous sodium sulfate
  14. filtrationfiltered
  15. concentrationconcentrated

Sources & evidence

ORD record
ord-7111a26ca1504127aab6da0869872ffd
Source dataset
uspto-grants-2011_09
Patent number
US08012956B2

Reaction notes

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