Sodium Hydroxide → tert-Butyl 5-(hydroxymethyl)pyridin-2-ylcarbamate

HRID 2301321Notes

Reaction equation

HRID 2301321 reaction equation
[H-].[Al+3].[Li+].[H-].[H-].[H-].[C:7]([O:11][C:12]([NH:14][C:15]1[CH:25]=[CH:24][C:18]([C:19](OCC)=[O:20])=[CH:17][N:16]=1)=[O:13])([CH3:10])([CH3:9])[CH3:8].[OH-].[Na+].S([O-])([O-])(=O)=O.[Mg+2]>C(OCC)C.O1CCCC1.O>[C:7]([O:11][C:12]([NH:14][C:15]1[N:16]=[CH:17][C:18]([CH2:19][OH:20])=[CH:24][CH:25]=1)=[O:13])([CH3:10])([CH3:8])[CH3:9]

Participants

8

Reactant 4

HCID 14798Sodium HydroxideHCID 24083Sulfuric acid magnesium salt (1:1)HCID 21226445Aluminium lithium hydrideHCID 21879719Ethyl 6-(((tert-butoxy)carbonyl)amino)pyridine-3-carboxylate

Product 1

HCID 3575389tert-Butyl 5-(hydroxymethyl)pyridin-2-ylcarbamateYield 89.2%

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To 4.6 mL(4.6 mmol) of a 1M solution of lithium aluminum hydride in diethyl ether at −40 C. under a nitrogen atmosphere, was added a solution of 618 mg(2.3 mmol) of ethyl 6-(tert-butyloxycarbonylamino)nicotinate from part B in 40 mL of anhydrous tetrahydrofuran. After the addition, this was warmed to room temperature, stirred for 3 hours, cooled to 0 C., and 145 μL of water, 145 μL of 20% sodium hydroxide solution and 290 μL of water were successively added. To the resulting mixture was added 50 mL of tetrahydrofuran and stirring continued for 30 minutes. Anhydrous magnesium sulfate was added, the solids removed via filtration and the filtrate concentrated under reduced pressure to afford 460 mg of the desired product, m/e=224(M+), which was used directly in the next step.

Workup

  1. additionAfter the addition
  2. temperaturecooled to 0 C
  3. stirringstirring
  4. waitcontinued for 30 minutes
  5. customthe solids removed via filtration
  6. concentrationthe filtrate concentrated under reduced pressure

Sources & evidence

ORD record
ord-740b8ec2e6444391b7b1042028b1f0fb
Source dataset
uspto-grants-2002_12
Patent number
US06500832B1

Reaction notes

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