Toluene → HCID 9967052, compound

HRID 494880Notes

Reaction equation

HRID 494880 reaction equation
CS(O[CH2:6][CH2:7][C:8]1[O:9][C:10]2[CH:16]=[CH:15][C:14]([C:17]3[C:18]([CH3:23])=[N:19][O:20][C:21]=3[CH3:22])=[CH:13][C:11]=2[CH:12]=1)(=O)=O.[CH3:24][C@@H:25]1[CH2:29][CH2:28][CH2:27][NH:26]1.C1(C)C=CC=CC=1.[OH-].[Na+]>C(#N)C.[Cl-].[Na+].O>[CH3:23][C:18]1[C:17]([C:14]2[CH:15]=[CH:16][C:10]3[O:9][C:8]([CH2:7][CH2:6][N:26]4[CH2:27][CH2:28][CH2:29][C@H:25]4[CH3:24])=[CH:12][C:11]=3[CH:13]=2)=[C:21]([CH3:22])[O:20][N:19]=1

Participants

7

Reactant 4

HCID 1140TolueneHCID 14798Sodium HydroxideHCID 641544(R)-2-MethylpyrrolidineHCID 22274413HCID 22274413, compound

Product 1

HCID 9967052HCID 9967052, compoundYield 69%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

A 3.3 mL (1 mmol) aliquot of the product from Example 161B in 8.33 mL of acetonitrile was transferred to a separate flask. Mono-(L)-tartaric acid salt of (R)-2-methylpyrrolidine (0.82 g, 3.5 mmol) was converted to the free base by shaking with 1 mL of toluene, 0.5 mL of 50% wt/vol sodium hydroxide, and 2 mL of brine. After separating, the toluene layer was decanted by pipette and added to the 3.3 mL aliquot of the product from Example 16 1B. After stirring for one week at room temperature, the reaction was poured into dichloromethane and washed with aqueous ammonia, dried over sodium sulfate, and purified by flash chromatography, eluting with 97:3 dichloromethane/methanol/0.1% NH3, to give 225 mg (69%) of the title compound as a clear oil. MS (DCI) m/z 325.2 (M+H)+; 1HNMR (300 MHz, CDCl3) δ 1.18 (d, 1H, J=6.3 Hz), 2.24 (s, 3H), 2.40 (s, 3H), 1.5-2.0 (m, 6H), 2.5 (m, 1H), 3.02 (t, 2H, J=7.5 Hz), 3.23 (m, 2H), 6.48 (s, 1H), 7.08 (dd, 1H, J=9.0, 2.1 Hz), 7.34 (d, 1H, J=2.1 Hz), 7.44 (d, 1H, 9.0 Hz).

Workup

  1. customAfter separating
  2. customthe toluene layer was decanted by pipette
  3. additionadded to the 3.3 mL aliquot of the product from Example 16 1B
  4. additionthe reaction was poured into dichloromethane
  5. washwashed with aqueous ammonia
  6. dry with materialdried over sodium sulfate
  7. custompurified by flash chromatography
  8. washeluting with 97:3 dichloromethane/methanol/0.1% NH3

Sources & evidence

ORD record
ord-fc2bc2c2f67e42d3bb479e956ad2f825
Source dataset
uspto-grants-2009_05
Patent number
US07538138B2

Reaction notes

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