HCID 67972215, compound → HCID 67972560, compound

HRID 1804614Notes

Reaction equation

HRID 1804614 reaction equation
[C:1]([C:3]([N:12]1[CH2:17][CH2:16][N:15]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:14][CH2:13]1)([C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[F:11])[CH3:4])#N.C[Mg]Br>O1CCCC1>[F:11][C:6]1[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=1[C:3]([N:12]1[CH2:13][CH2:14][N:15]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:16][CH2:17]1)([CH3:4])[CH3:1]

Participants

4

Reactant 2

HCID 67972215HCID 67972215, compoundHCID 178418573HCID 178418573, compound

Product 1

HCID 67972560HCID 67972560, compoundYield 69%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a stirred solution of 0.60 g (1.8 mmol) of the title compound from Step A above in 10 mL of anhydrous tetrahydrofuran cooled to 0° C. under a nitrogen atmosphere was added 3.0 mL (9.0 mmol) of a 3.0 M methyl magnesium bromide solution in tetrahydrofuran. The resulting mixture was allowed to warm to ambient temperature over 8 h then quenched with water. The layers were separated and the aqueous phase extracted with ethyl acetate. The combined organic layers were washed with brine, dried over magnesium sulfate, filtered and evaporated in vacuo. The residue was purified by silica gel chromatography eluting with a 0-100% ethyl acetate in hexanes gradient to afford the title compound as a yellow gum (0.40 g, 69% yield). (500 MHz, CDCl3) δ 7.56 (td, J=8.1, 1.7 Hz, 1H), 7.21-7.16 (m, 1H), 7.06 (t, J=8.1, 1H), 6.97 (dd, J=12.7, 8.1 Hz, 1H), 3.40-3.38 (m, 4H), 2.45 (br s, 4H), 1.44 (s, 9H), 1.43 (s, 3H), 1.42 (s, 3H). LC-MS: m/z (ES) 323.0 (MH)+.

Workup

  1. customthen quenched with water
  2. customThe layers were separated
  3. extractionthe aqueous phase extracted with ethyl acetate
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. customevaporated in vacuo
  8. customThe residue was purified by silica gel chromatography
  9. washeluting with a 0-100% ethyl acetate in hexanes gradient

Sources & evidence

ORD record
ord-7c230b8e696847689fde8bdf88462527
Source dataset
uspto-grants-2013_01
Patent number
US08354403B2

Reaction notes

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