Hydrochloric Acid → HCID 86677870, compound

HRID 1499954Notes

Reaction equation

HRID 1499954 reaction equation
[Cl:1][C:2]1[C:3]([F:23])=[C:4]([CH:17]2[CH2:21][NH:20][C:19](=[O:22])[CH2:18]2)[C:5]([O:14][CH2:15][CH3:16])=[C:6]([C:8]2([CH3:13])OCC[O:9]2)[CH:7]=1.Cl.O>CO>[C:8]([C:6]1[C:5]([O:14][CH2:15][CH3:16])=[C:4]([CH:17]2[CH2:21][NH:20][C:19](=[O:22])[CH2:18]2)[C:3]([F:23])=[C:2]([Cl:1])[CH:7]=1)(=[O:9])[CH3:13]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 962WaterHCID 86677871HCID 86677871, compound

Product 1

HCID 86677870HCID 86677870, compoundYield 100.1%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
20 °C

Procedure

The separated enantiomers from step 4 were each processed individually to the final compounds. A solution of 4-[3-chloro-6-ethoxy-2-fluoro-5-(2-methyl-1,3-dioxolan-2-yl)phenyl]pyrrolidin-2-one (1.7 g, 5.0 mmol) (from Step 4) in methanol (17 mL) was treated with 6.0 M hydrogen chloride in water (11 mL, 69 mmol) dropwise and stirred 20° C. for 30 min. The reaction mixture was added dropwise to ice cooled saturated sodium bicarbonate solution (75 ml) and extracted with ethyl acetate (2×100 ml). The combined organic extracts were washed with brine, dried over sodium sulfate, filtered, and concentrated to give the desired products [from peak 1 (1.5 g, 99%); from peak 2 (1.5 g, 99%)] that were used without further purification. From peak 1: 1H NMR (400 MHz, DMSO-d6) δ 7.84 (s, 1H), 7.70 (d, J=8.6 Hz, 1H), 4.16-3.99 (m, 1H), 3.83 (q, J=7.0 Hz, 2H), 3.65-3.54 (m, 1H), 3.30-3.23 (m, 1H), 2.55 (s, 3H), 2.33 (dd, J=16.8, 8.4 Hz, 1H), 1.30 (t, J=7.0 Hz, 3H). LCMS for C14H16ClFNO3 (M+H)+: m/z=300.1; Found: 300.0. From peak 2: 1H NMR (400 MHz, DMSO-d6) δ 7.84 (s, 1H), 7.70 (d, J=8.6 Hz, 1H), 4.13-4.00 (m, 1H), 3.87-3.77 (m, 2H), 3.65-3.55 (m, 1H), 3.31-3.23 (m, 1H), 2.55 (s, 3H), 2.32 (ddd, J=16.9, 8.4, 1.6 Hz, 1H), 1.30 (t, J=7.0 Hz, 3H). LCMS for C14H16ClFNO3 (M+H)+: m/z=300.1; Found: 300.1.

Workup

  1. extractionextracted with ethyl acetate (2×100 ml)
  2. washThe combined organic extracts were washed with brine
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-7376734290174cf88902a936e434a8ac
Source dataset
uspto-grants-2015_12
Patent number
US09199982B2

Reaction notes

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