Sodium Bicarbonate → Tert-butyl 4-(2-(tert-butoxycarbonyl)hydrazinyl)piperidine-1-carboxylate

HRID 1931583Notes

Reaction equation

HRID 1931583 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11](=[N:14][NH:15][C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[BH4-].[Na+].C(=O)(O)[O-].[Na+]>CO.O1CCCC1.[Cl-].[Na+].O>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([NH:14][NH:15][C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 3

HCID 516892Sodium BicarbonateHCID 4311764Sodium borohydrideHCID 20824233Tert-butyl 4-[(tert-butoxycarbonyl)hydrazono]piperidine-1-carboxylate

Product 1

HCID 20824232Tert-butyl 4-(2-(tert-butoxycarbonyl)hydrazinyl)piperidine-1-carboxylateYield 99.3%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
60 °C

Procedure

A solution of 4-(tert-butoxycarbonyl-hydrazono)-piperidine-1-carboxylic acid tert-butyl ester (from Step 1; 12.0 g, 38.3 mmol) in methanol (60 mL) and tetrahydrofuran (120 mL) was cooled to 0° C. Sodium borohydride (9.0 g, 238 mmol) was added slowly in three portions in 15-30 min intervals. The reaction mixture was heated to 60° C. for 2 h and then cooled to room temperature. A solution of 20% brine (90.0 mL) and 10% sodium bicarbonate (200 mL) were slowly added to the stirred reaction mixture. The organic layer was separated and the aqueous layer was extracted with methyl tert-butyl ether (2×50 mL). The combined organic layers were washed with brine (3×50 mL) and concentrated. To the residue was added acetonitrile (15 mL). The mixture was concentrated again to remove trace amounts of water, to give 4-(tert-butoxycarbonyl-hydrazino)-piperidine-1-carboxylic acid tert-butyl ester (12.0 g, 99%) as a white solid. 1H NMR (CDCl3) δ 1.27 (m, 2H), 1.44 (s, 18H), 1.76 (m, 2H), 2.84 (t, 2H, J=11.7 Hz), 3.00 (m, 1H), 3.95 (m, 3H), 6.03 (br, 1H).

Workup

  1. temperaturecooled to room temperature
  2. customThe organic layer was separated
  3. extractionthe aqueous layer was extracted with methyl tert-butyl ether (2×50 mL)
  4. washThe combined organic layers were washed with brine (3×50 mL)
  5. concentrationconcentrated
  6. additionTo the residue was added acetonitrile (15 mL)
  7. concentrationThe mixture was concentrated again
  8. customto remove trace amounts of water

Sources & evidence

ORD record
ord-276018be46a848b29bdf9d289cbf43b7
Source dataset
uspto-grants-2012_05
Patent number
US08188098B2

Reaction notes

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