Ammonium Chloride → HCID 25008645, compound

HRID 2093201Notes

Reaction equation

HRID 2093201 reaction equation
[CH3:1][Mg+].[Br-].[C:4]([C:7]1[CH:12]=[CH:11][C:10]([C:13]2[CH:14]=[C:15]([C:20]3[CH:25]=[CH:24][C:23]([C:26]([F:29])([F:28])[F:27])=[CH:22][C:21]=3[CH2:30][N:31]3[C@@H:35]([CH3:36])[C@@H:34]([C:37]4[CH:42]=[C:41]([C:43]([F:46])([F:45])[F:44])[CH:40]=[C:39]([C:47]([F:50])([F:49])[F:48])[CH:38]=4)[O:33][C:32]3=[O:51])[C:16]([Cl:19])=[CH:17][CH:18]=2)=[C:9]([CH3:52])[CH:8]=1)(=[O:6])[CH3:5].[Cl-].[NH4+]>C1COCC1>[F:44][C:43]([F:46])([F:45])[C:41]1[CH:42]=[C:37]([C@H:34]2[O:33][C:32](=[O:51])[N:31]([CH2:30][C:21]3[CH:22]=[C:23]([C:26]([F:27])([F:28])[F:29])[CH:24]=[CH:25][C:20]=3[C:15]3[C:16]([Cl:19])=[CH:17][CH:18]=[C:13]([C:10]4[CH:11]=[CH:12][C:7]([C:4]([OH:6])([CH3:1])[CH3:5])=[CH:8][C:9]=4[CH3:52])[CH:14]=3)[C@H:35]2[CH3:36])[CH:38]=[C:39]([C:47]([F:49])([F:50])[F:48])[CH:40]=1

Participants

5

Reactant 3

HCID 25517Ammonium ChlorideHCID 25008473HCID 25008473, compoundHCID 178418689HCID 178418689, compound

Product 1

HCID 25008645HCID 25008645, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

MeMgBr (0.168 ml, 0.168 mmol, 1 M solution) was added to a solution of ketone from Example 52 (80 mg, 0.112 mmol) in THF (3 ml) at −78° C. The solution was stirred at −78° C. for 2 h. Saturated ammonium chloride solution was added. The mixture was extracted with EtOAc (3×10 ml). The combined EtOAc layers were washed with brine, and dried over sodium sulfate. The residue was purified by flash column on silica gel, eluting with EtOAc/hexane (30:70) to give the title compound as a colorless solid. 1H NMR (CDCl3, 500 MHz): δ a mixture of 1:1 atopoisomers 7.89 (s, 2H), 7.83 (d, J=8 Hz, 1H), 7.72 (m, 4H), 7.63 (d, J=8.5 Hz, 1H), 7.51 (d, J=8.0 Hz, 0.5H), 7.46 (d, J=8.0 Hz, 0.5H), 7.40-7.34 (m, 2H), 7.27 (d, J=2.0 Hz, 0.5H), 7.21 (d, J=2.5 Hz, 0.5H), 5.64 (d, J=8.0 Hz, 0.5H), 5.63 (d, J=8.0 Hz, 0.5H), 5.02 (d, J=16.0 Hz, 0.5H), 4.83 (d, J=16.0 Hz, 0.5H), 4.08 (d, J=16.0 Hz, 0.5H), 4.01 (d, J=15.5 Hz, 0.5H), 4.00 (m, 0.5H), 3.90(m, 0.5H), 2.41 (s, 1.5H), 2.39 (s, 1.5H), 1.60 (m, 3H), 1.28 (m, 3H), 0.64 (d, J=6.5 Hz, 1.5H), 0.62 (d, J=6.5 Hz, 1.5H).

Workup

  1. extractionThe mixture was extracted with EtOAc (3×10 ml)
  2. washThe combined EtOAc layers were washed with brine
  3. dry with materialdried over sodium sulfate
  4. customThe residue was purified by flash column on silica gel
  5. washeluting with EtOAc/hexane (30:70)

Sources & evidence

ORD record
ord-1294223402f24a20ab4edd39ed1725f0
Source dataset
uspto-grants-2013_05
Patent number
US08440702B2

Reaction notes

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