Hydrochloric Acid → 2-(4-fluoro-phenyl)-4-oxo-5-triisopropylsilanyl-3,4-dihydro-2H-pyridine-1-carboxylic acid 5-methyl-2-(1-methyl-1-phenyl-ethyl)-cyclohexyl ester

HRID 1691798Notes

Reaction equation

HRID 1691798 reaction equation
C[O:2][C:3]1[CH:8]=[CH:7][N:6]=[CH:5][C:4]=1[Si:9]([CH:16]([CH3:18])[CH3:17])([CH:13]([CH3:15])[CH3:14])[CH:10]([CH3:12])[CH3:11].Cl[C:20]([O:22][CH:23]1[CH2:28][CH:27]([CH3:29])[CH2:26][CH2:25][CH:24]1[C:30]([CH3:38])([C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)[CH3:31])=[O:21].[F:39][C:40]1[CH:45]=[CH:44][C:43]([Mg]Br)=[CH:42][CH:41]=1.C1COCC1.Cl>C1(C)C=CC=CC=1>[CH3:29][CH:27]1[CH2:28][CH:23]([O:22][C:20]([N:6]2[CH:5]=[C:4]([Si:9]([CH:16]([CH3:17])[CH3:18])([CH:13]([CH3:14])[CH3:15])[CH:10]([CH3:11])[CH3:12])[C:3](=[O:2])[CH2:8][CH:7]2[C:43]2[CH:44]=[CH:45][C:40]([F:39])=[CH:41][CH:42]=2)=[O:21])[CH:24]([C:30]([CH3:38])([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[CH3:31])[CH2:25][CH2:26]1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 8028TetrahydrofuranHCID 109015244-Methoxy-3-(triisopropylsilyl)pyridineHCID 145714908-Phenylmenthol chloroformateHCID 178418676HCID 178418676, compound

Product 1

HCID 669062662-(4-fluoro-phenyl)-4-oxo-5-triisopropylsilanyl-3,4-dihydro-2H-pyridine-1-carboxylic acid 5-methyl-2-(1-methyl-1-phenyl-ethyl)-cyclohexyl esterYield 48%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Conditions

Temperature
-78 °C

Procedure

Following the procedure reported in JACS 1994, 116, 4719-4728, to a solution of 4-methoxy-3-triisopropylsilanyl-pyridine (6.06 g, 22.8 mmol) in toluene (160 mL) at −25° C. was added a solution of 5-methyl-2-(1-methyl-1-phenyl-ethyl)-cyclohexyl chloroformate (6.73 g, 26.2 mmol) in toluene (140 mL). After 15 minutes the mixture was cooled to −78° C. and 1.0M 4-fluorophenyl magnesium bromide in THF (26.1 mL, 26.2 mmol) was added slowly. The mixture was stirred at −78° C. for 1 hour. 2N HCl was added and the mixture was allowed to warm to room temperature and was stirred for additional 15 minutes. The mixture was extracted with ethyl acetate, washed with water and brine, dried over MgSO4, filtered and concentrated to dryness. Purification of the residue by flash chromatography (hexane/ethyl acetate 9:1) gave 2-(4-fluoro-phenyl)-4-oxo-5-triisopropylsilanyl-3,4-dihydro-2H-pyridine-1-carboxylic acid 5-methyl-2-(1-methyl-1-phenyl-ethyl)-cyclohexyl ester (1.06 g, 48%) as a white solid.

Workup

  1. temperatureto warm to room temperature
  2. stirringwas stirred for additional 15 minutes
  3. extractionThe mixture was extracted with ethyl acetate
  4. washwashed with water and brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated to dryness
  8. customPurification of the residue by flash chromatography (hexane/ethyl acetate 9:1)

Sources & evidence

ORD record
ord-22b8ca4a11484e618f70758f536a2bff
Source dataset
uspto-grants-2012_04
Patent number
US08153809B2

Reaction notes

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