Methanol → 6-(4-((Tert-butoxy)carbonyl)piperazin-1-yl)pyridine-3-carboxylic acid

HRID 906073Notes

Reaction equation

HRID 906073 reaction equation
C([O:3][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])C.CO.[OH-].[Na+]>C1COCC1>[C:21]([O:20][C:18]([N:15]1[CH2:16][CH2:17][N:12]([C:9]2[CH:8]=[CH:7][C:6]([C:4]([OH:5])=[O:3])=[CH:11][N:10]=2)[CH2:13][CH2:14]1)=[O:19])([CH3:24])([CH3:22])[CH3:23]

Participants

5

Reactant 3

HCID 887MethanolHCID 14798Sodium Hydroxide2×HCID 31537267Tert-butyl 4-(5-(ethoxycarbonyl)pyridin-2-yl)piperazine-1-carboxylate

Product 1

HCID 27718236-(4-((Tert-butoxy)carbonyl)piperazin-1-yl)pyridine-3-carboxylic acidYield 59.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

tert-Butyl 4-(5-(ethoxycarbonyl)pyridin-2-yl)piperazine-1-carboxylate (3.65 g, 10.9 mmol) was taken into methanol (40 mL) followed by addition of 1M aqueous sodium hydroxide (15 mL) and THF (15 mL), and the mixture was heated at 50° C. for one hour. An additional portion of 1 M aqueous sodium hydroxide (10 mL) was then added and heating was continued an additional two hours. The mixture was then cooled to room temperature and concentrated to remove organic solvents. The aqueous residue was partitioned with ethyl ether and the organic layer was discarded. The aqueous phase has carefully brought to pH 5-6 by addition of 1M aqueous hydrochloric acid to give a thick white suspension. The solid was collected by filtration and dried to give 6-(4-(tert-butoxycarbonyl)piperazin-1-yl)nicotinic acid (2.0 g). 1H NMR (400 MHz, DMSO-d6): 12.57 (br s, 1H), 8.64 (s, 1H), 7.95 (d, 1H), 6.86 (d, 1H), 3.67-3.62 (m, 4H), 3.45-3.40 (m, 4H), 1.43 (s, 9H).

Workup

  1. temperatureheating
  2. temperatureThe mixture was then cooled to room temperature
  3. concentrationconcentrated
  4. customto remove organic solvents
  5. customThe aqueous residue was partitioned with ethyl ether
  6. additionThe aqueous phase has carefully brought to pH 5-6 by addition of 1M aqueous hydrochloric acid
  7. customto give a thick white suspension
  8. filtrationThe solid was collected by filtration
  9. customdried

Sources & evidence

ORD record
ord-afe19df729c14f809a89994f345a22ea
Source dataset
uspto-grants-2011_09
Patent number
US08012956B2

Reaction notes

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