Water → HCID 12132838, compound

HRID 46019Notes

Reaction equation

HRID 46019 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[C@H:8]([C@H:12]([CH2:16][CH3:17])[C:13]([OH:15])=[O:14])[CH2:7][CH2:6]2.[C:18]([O-])(O)=O.[Na+].CI.O>CN(C=O)C>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[C@H:8]([C@H:12]([CH2:16][CH3:17])[C:13]([O:15][CH3:18])=[O:14])[CH2:7][CH2:6]2

Participants

6

Reactant 4

HCID 962WaterHCID 6328Methyl iodide2×HCID 516892Sodium BicarbonateHCID 11345339(2S)-2-[(1S)-5-methoxy-2,3-dihydro-1H-inden-1-yl]butanoic Acid

Product 1

HCID 12132838HCID 12132838, compoundYield 99.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A suspension of acid prepared in Example 4 (220.0 g, 0.94 mol), NaHCO3 (237.0 g, 2.82 mol), CH3I (200 g, 1.41 mol) in 2.0 L DMF was stirred under Ar at rt for 18 hours. NMR analysis showed 95% reaction. Adding CH3I (100 g), and stirring for additional 24 hours at rt caused completion of the reaction. The reaction mixture was poured into 4.0 L water, and extracted with EtOAc (2×2 L). The organic layer was sequentially washed with water (2×1 L), 1 L of 1N NaOH solution, water (2×1 L), and 500 mL brine, and dried over Na2SO4. The product (233 g, 99%) was obtained as a light yellow oil after solvent removal and vacuum drying. 1H NMR (DMSO-d6) δ 6.90 (d, 1H), 6.78 (d, 1H), 6.66 (dd, 1H), 3.70 (s, 3H), 3.60 (s, 3H), 3.20 (m, 1H), 2.80 (m, 2H), 2.40 (m, 1H), 2.08 (m, 1H), 1.80 (m, 1H), 1.58 (m, 1H), 1.40 (m, 1H), 0.80 (t, 3H).

Workup

  1. custom95% reaction
  2. customcompletion of the reaction
  3. extractionextracted with EtOAc (2×2 L)
  4. washThe organic layer was sequentially washed with water (2×1 L), 1 L of 1N NaOH solution, water (2×1 L), and 500 mL brine
  5. dry with materialdried over Na2SO4

Sources & evidence

ORD record
ord-c1b28fc85f0d4536b34bb9a5394911c5
Source dataset
uspto-grants-2013_09
Patent number
US08541618B2

Reaction notes

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