Diisopropylamine → HCID 69450603, compound

HRID 860165Notes

Reaction equation

HRID 860165 reaction equation
[Li][CH2:2][CH2:3][CH2:4][CH3:5].N(C(C)C)C(C)C.[CH3:13][N:14]1[CH:18]=[CH:17][CH:16]=[N:15]1.C([O:23][C:24]([N:26]1[CH2:31][CH:30]=[C:29](OS(C(F)(F)F)(=O)=O)[CH2:28][CH2:27]1)=[O:25])(C)(C)C>CCCCCC.C1COCC1.[Cl-].[Cl-].[Zn+2].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:2]([O:25][C:24]([N:26]1[CH2:27][CH:28]=[C:29]([C:18]2[N:14]([CH3:13])[N:15]=[CH:16][CH:17]=2)[CH2:30][CH2:31]1)=[O:23])[CH2:3][CH2:4][CH3:5]

Participants

9

Reactant 4

HCID 7912DiisopropylamineHCID 702551H-Pyrazole, 1-methyl-HCID 10991161Tert-butyl 4-(trifluoromethanesulfonyloxy)-1,2,3,6-tetrahydropyridine-1-carboxylateHCID 178418339Butyllithium

Product 1

HCID 69450603HCID 69450603, compoundYield 931.4%

Reagents, catalysts & solvents 4

HCID 3007855ZincchlorideCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent3×HCID 8058HexaneSolvent

Conditions

Temperature
-78 °C

Procedure

A solution of BuLi (13.3 mmol) in hexane (1.6 M, 8.3 mL) was added to a stirred solution of iPr2NH (1.87 mL, 13.3 mmol) in THF (15 mL) at 0° C. under N2. The resulting solution was stirred for 20 min and then cooled to −78° C. and N-methyl pyrazole (0.99 g, 12.1 mmol) was added. The mixture was stirred for 1 h at −78° C. and then a solution of ZnCl2 (1.8 g, 13.3 mmol) in THF (10 mL) was added and the reaction was allowed to warm to RT and stirred for a further 20 min. A solution of 1-(tert-butoxycarbonyl)-4-[(trifluoromethanesulfonyl)oxy]-1,2,3,6-tetrahydropyridine (Synthesis 1991, 11, 993–5) (150 mg, 0.53 mmol) in THF (5 mL) and Pd(PPh3)4 (347 mg, 5 mol %) were added and the reaction was heated at reflux for 3 h. The mixture was partitioned between EtOAc (75 mL) and NH4Cl solution (75 mL), separated and the organics were washed with H2O (75 mL) and brine (50 mL). After concentrating under reduced pressure, the residue was purified by column chromatography on silica eluting with 100% EtOAc to yield the pyrazole (1.30 g, 82%). 1H NMR (CDCl3, 360 MHz) δ 7.41 (1H, d, J=1.9 Hz), 6.13 (1H, d, J=1.9 Hz), 5.83 (1H, broad s), 4.10–4.00 (2H, m), 3.88 (3H, s), 3.62 (2H, t, J=5.7 Hz), 2.45–2.37 (2H, m), 1.49 (9H, s). MS (ES+) C14H21N3O2 requires: 263, found: 264 (M+H+, 100%).

Workup

  1. stirringThe mixture was stirred for 1 h at −78° C.
  2. temperatureto warm to RT
  3. stirringstirred for a further 20 min
  4. temperaturethe reaction was heated
  5. temperatureat reflux for 3 h
  6. customThe mixture was partitioned between EtOAc (75 mL) and NH4Cl solution (75 mL)
  7. customseparated
  8. washthe organics were washed with H2O (75 mL) and brine (50 mL)
  9. concentrationAfter concentrating under reduced pressure
  10. customthe residue was purified by column chromatography on silica eluting with 100% EtOAc

Sources & evidence

ORD record
ord-0a3520f97b7d49e198dd8ebb62cc25a8
Source dataset
uspto-grants-2006_12
Patent number
US07153868B2

Reaction notes

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