Benzyl Bromide → 1-Benzyl-4-(1,3-diethyl-5-methyl-pyrazol-4-yl)-1,2,3,6-tetrahydropyridine

HRID 1245588Notes

Reaction equation

HRID 1245588 reaction equation
[CH2:1]([N:3]1[C:7]([CH3:8])=[C:6]([C:9]2[CH:14]=[CH:13][N:12]=[CH:11][CH:10]=2)[C:5]([CH2:15][CH3:16])=[N:4]1)[CH3:2].[CH2:17](Br)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.[BH4-].[Na+]>CO>[CH2:17]([N:12]1[CH2:13][CH:14]=[C:9]([C:6]2[C:5]([CH2:15][CH3:16])=[N:4][N:3]([CH2:1][CH3:2])[C:7]=2[CH3:8])[CH2:10][CH2:11]1)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1

Participants

5

Reactant 3

HCID 7498Benzyl BromideHCID 4311764Sodium borohydrideHCID 219127864-(1,3-Diethyl-5-methyl-1H-pyrazol-4-yl)pyridine

Product 1

HCID 219127201-Benzyl-4-(1,3-diethyl-5-methyl-pyrazol-4-yl)-1,2,3,6-tetrahydropyridine

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 7.55 g (35.0 mmol) of 1,3-diethyl-4-(4-pyridyl)-5-methylpyrazole (from Step E) and 4.20 mL (35.0 mmol) of benzyl bromide in 50 mL of MeOH was heated at reflux for 30 min. The mixture was cooled to 0° C. and treated with 2.65 g (70.0 mmol) of sodium borohydride in portions so as to maintain the internal at ˜0° C. The resulting mixture was stirred cold for 30 min, then concentrated. The residue was partitioned between 300 mL of CH2Cl2 and 150 mL of 1.0 N NaOH and the layers were separated. The organic layer was dried over MgSO4. The organic layer was extracted with 300 mL of ether; the extract was dried over MgSO4. The organic layers were combined and concentrated. Chromatography on a Biotage 75L using 9:1 v/v heptane/acetone as the eluant affforded the title compound. 1H-NMR (400 MHz) δ 1.19 (t, J=7.6, 3H), 1.37 (t, J=7.6, 3H), 2.17 (s, 3H), 2.31–2.35 (m, 2H), 2.58 (q, J=7.6, 2H), 2.66 (t, J=5.6, 2H), 3.13 (app q, J=2.8, 2H), 3.65 (s, 2H), 4.01 (q, J=7.6, 2H), 5.46–5.48 (m, 1H), 7.26–7.39.

Workup

  1. temperatureat reflux for 30 min
  2. temperatureto maintain the internal at ˜0° C
  3. concentrationconcentrated
  4. customThe residue was partitioned between 300 mL of CH2Cl2 and 150 mL of 1.0 N NaOH
  5. customthe layers were separated
  6. dry with materialThe organic layer was dried over MgSO4
  7. extractionThe organic layer was extracted with 300 mL of ether
  8. dry with materialthe extract was dried over MgSO4
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-f0b61cc68bc449ad8c6be54ebaad47ac
Source dataset
uspto-grants-2006_10
Patent number
US07125887B2

Reaction notes

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