tert-Butyl 4-oxopiperidine-1-carboxylate → 1-(tert-Butoxycarbonyl)-4-hydroxy-4-(2-ethyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyridin-3-yl)piperidine

HRID 1245583Notes

Reaction equation

HRID 1245583 reaction equation
Br[C:2]1[C:3]([CH2:11][CH3:12])=[N:4][N:5]2[CH2:10][CH2:9][CH2:8][CH2:7][C:6]=12.[Li]C(C)(C)C.[O:18]=[C:19]1[CH2:24][CH2:23][N:22]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:21][CH2:20]1>C1COCC1>[C:28]([O:27][C:25]([N:22]1[CH2:23][CH2:24][C:19]([OH:18])([C:2]2[C:3]([CH2:11][CH3:12])=[N:4][N:5]3[CH2:10][CH2:9][CH2:8][CH2:7][C:6]=23)[CH2:20][CH2:21]1)=[O:26])([CH3:31])([CH3:29])[CH3:30]

Participants

5

Reactant 3

HCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 219127943-Bromo-2-ethyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyridineHCID 178418306HCID 178418306, compound

Product 1

HCID 219127551-(tert-Butoxycarbonyl)-4-hydroxy-4-(2-ethyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyridin-3-yl)piperidine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a solution of 3-bromo-2-ethyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyridine (4.01 g, 17.6 mmol, from Step C) in THF (20 mL) was added tert-BuLi (1.7 M in pentane, 22.8 mL, 38.7 mmol) dropwise at −78° C. After stirring at −78° C. for 30 min., was added tert-butyl 4-oxo-1-piperidinecarboxylate (3.51 g, 17.6 mmol) in THF (10 mL) dropwise at −78° C. The mixture was stirred at −78° C. for 10 min. and at rt for 4 h. After the reaction was quenched with aqueous NH4Cl, the mixture was partitioned between EtOAc and water. Aqueous layer was extracted with EtOAc (3×). Combined organic phase was washed with brine and dried over anhydrous MgSO4. Concentration was followed by purification by flash chromatography (hexanes:EtOAc=1:1, then 100% EtOAc) to give the title compound as a foamy solid. 1HNMR (500 MHz, CDCl3) δ 1.26 (t, 3H, J=7.4 Hz), 1.49 (s, 9H), 1.75–1.90 (m, 4H), 1.90–2.10 (m, 4H), 2.76 (q, 2H, J=7.6 Hz), 2.89 (t, 2H, J=6.4 Hz), 3.10–3.20 (br, 2H), 3.85–4.05 (br, 2H), 4.09 (t, 2H, J=6.2 Hz). ESI-MS 276 (M-tert-Bu-H2O+H); HPLC A 2.05 min.

Workup

  1. stirringThe mixture was stirred at −78° C. for 10 min. and at rt for 4 h
  2. customAfter the reaction was quenched with aqueous NH4Cl
  3. customthe mixture was partitioned between EtOAc and water
  4. extractionAqueous layer was extracted with EtOAc (3×)
  5. washCombined organic phase was washed with brine
  6. dry with materialdried over anhydrous MgSO4
  7. concentrationConcentration
  8. customwas followed by purification by flash chromatography (hexanes

Sources & evidence

ORD record
ord-1a8c97d85bdd499f97d6a943c331df23
Source dataset
uspto-grants-2006_10
Patent number
US07125887B2

Reaction notes

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