HCID 89421013, compound → HCID 71288448, compound

HRID 246276Notes

Reaction equation

HRID 246276 reaction equation
[F:1][C:2]([F:19])([F:18])[O:3][C:4]1[CH:5]=[C:6](/[CH:10]=[N:11]/[S@:12]([C:14]([CH3:17])([CH3:16])[CH3:15])=[O:13])[CH:7]=[CH:8][CH:9]=1.[CH3:20][Mg]Br>C1COCC1>[F:19][C:2]([F:1])([F:18])[O:3][C:4]1[CH:5]=[C:6]([C@H:10]([NH:11][S@:12]([C:14]([CH3:16])([CH3:15])[CH3:17])=[O:13])[CH3:20])[CH:7]=[CH:8][CH:9]=1

Participants

4

Reactant 2

HCID 89421013HCID 89421013, compoundHCID 178418573HCID 178418573, compound

Product 1

HCID 71288448HCID 71288448, compoundYield 50.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-76 °C

Procedure

In a round-bottomed flask, (S)-2-methyl-propane-2-sulfinic acid 1-(3-trifluoromethoxyphenyl)-meth-(E)-ylideneamide (424 mg, 1.45 mmol) was dissolved in THF (2.9 ml). The light yellow solution was cooled to −76° C. and methylmagnesium bromide (3.0 M in diethyl ether, 0.86 ml, 2.58 mmol) was added dropwise. The reaction mixture was allowed to warm slowly to room temperature overnight then quenched with saturated aqueous NH4Cl and extracted with EtOAc (2×). The combined organic layers were washed with water and brine then dried over sodium sulfate, filtered and concentrated. The residue was chromatographed over silica gel with EtOAc/hexanes (gradient: 0-10% EtOAc) to give 225 mg (50%) of (S)-2-methyl-propane-2-sulfinic acid [(R)-1-(3-trifluoromethoxy-phenyl)-ethyl]-amide as a colorless oil. 1H NMR (CDCl3, 400 MHz): δ (ppm) 7.33-7.41 (m, 1H), 7.24-7.28 (m, 1H), 7.22 (s, 1H), 7.13 (dd, J=8.1, 1.0 Hz, 1H), 4.62 (q, J=6.7 Hz, 1H), 1.55 (d, J=6.6 Hz, 3H), 1.22 (s, 9H). Also isolated 161 mg (36%) of (S)-2-methyl-propane-2-sulfinic acid [(S)-1-(3-trifluoromethoxy-phenyl)ethyl]-amide as a colorless oil. 1H NMR (CDCl3, 400 MHz): δ (ppm) 7.35-7.43 (m, 1H), 7.28-7.33 (m, 1H), 7.21 (s, 1H), 7.11-7.18 (m, 1H), 4.58 (qd, J=6.4, 2.9 Hz, 1H), 1.53 (d, J=6.6 Hz, 3H), 1.25 (s, 9H).

Workup

  1. temperatureto warm slowly to room temperature overnight
  2. customthen quenched with saturated aqueous NH4Cl
  3. extractionextracted with EtOAc (2×)
  4. washThe combined organic layers were washed with water and brine
  5. dry with materialthen dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was chromatographed over silica gel with EtOAc/hexanes (gradient: 0-10% EtOAc)

Sources & evidence

ORD record
ord-b73f3e63668f4cbdbaefdc05856fb678
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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