Hydrochloric Acid → HCID 89656488, compound

HRID 930914Notes

Reaction equation

HRID 930914 reaction equation
[F:1][C:2]1[CH:31]=[C:30]([F:32])[CH:29]=[CH:28][C:3]=1[O:4][C:5]1[CH:10]=[CH:9][C:8]([S:11]([CH3:14])(=[O:13])=[O:12])=[CH:7][C:6]=1[C:15]1[C:16]2[CH:25]=[C:24]([CH:26]=[O:27])[NH:23][C:17]=2[C:18](=[O:22])[N:19]([CH3:21])[CH:20]=1.[CH3:33][Mg]Br.Cl>O1CCCC1>[F:1][C:2]1[CH:31]=[C:30]([F:32])[CH:29]=[CH:28][C:3]=1[O:4][C:5]1[CH:10]=[CH:9][C:8]([S:11]([CH3:14])(=[O:12])=[O:13])=[CH:7][C:6]=1[C:15]1[C:16]2[CH:25]=[C:24]([CH:26]([OH:27])[CH3:33])[NH:23][C:17]=2[C:18](=[O:22])[N:19]([CH3:21])[CH:20]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 89657403HCID 89657403, compoundHCID 178418573HCID 178418573, compound

Product 1

HCID 89656488HCID 89656488, compoundYield 24.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of Example 278a (0.20 g, 0.44 mmol) in tetrahydrofuran (6 mL) at 0° C. was added methylmagnesium bromide (1.0 M in tetrahydrofuran, 0.873 mL, 0.873 mmol). The reaction mixture was stirred at 0° C. for one hour, and then 1M aqueous HCl (2 mL) was added. The reaction mixture was concentrated and partitioned between saturated aqueous sodium chloride (10 mL) and ethyl acetate (2×30 mL). The combined organic phase was washed with saturated aqueous sodium chloride (30 mL), dried over anhydrous sodium sulfate, filtered, and concentrated. The residue was purified by preparative thin layer chromatography (silica gel, dichloromethane/methanol, 15/1) to provide the title compound (51 mg, 24% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 11.83 (s, 1H), 7.96 (d, J=2.4 Hz, 1H), 7.86 (dd, J=2.4, 6.4 Hz, 1H), 7.55-7.50 (m, 1H), 7.42-7.36 (m, 2H), 7.20-7.15 (m, 1H), 6.97 (d, J=8.8 Hz, 1H), 6.15 (d, J=2 Hz, 1H), 5.13 (d, J=5.2 Hz, 1H), 4.80-4.77 (m, 1H), 3.57 (s, 3H), 3.25 (s, 3H), 1.38 (d, J=6.4 Hz, 3H). MS (ESI+) m/z 475.1 (M+1)+.

Workup

  1. concentrationThe reaction mixture was concentrated
  2. custompartitioned between saturated aqueous sodium chloride (10 mL) and ethyl acetate (2×30 mL)
  3. washThe combined organic phase was washed with saturated aqueous sodium chloride (30 mL)
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by preparative thin layer chromatography (silica gel, dichloromethane/methanol, 15/1)

Sources & evidence

ORD record
ord-733b089f79cc44eaa9e091e5303d41fd
Source dataset
uspto-grants-2016_03
Patent number
US09296741B2

Reaction notes

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