Dimethyl Sulfoxide → 2-Fluoro-6-[(3-methyl-5-methoxyphenyl)thio]benzonitrile

HRID 845

反応式

HRID 845 の反応式
Br[C:2]1[CH:3]=[C:4]([CH3:10])[CH:5]=[C:6]([O:8][CH3:9])[CH:7]=1.[Li]C(CC)C.[S].[F:17][C:18]1[CH:25]=[CH:24][CH:23]=[C:22](F)[C:19]=1[C:20]#[N:21].C[S:28](C)=O>C(=O)=O.CC(C)=O.O.C1COCC1>[F:17][C:18]1[CH:25]=[CH:24][CH:23]=[C:22]([S:28][C:2]2[CH:7]=[C:6]([O:8][CH3:9])[CH:5]=[C:4]([CH3:10])[CH:3]=2)[C:19]=1[C:20]#[N:21]

参加物

9

反応物 5

HCID 679Dimethyl SulfoxideHCID 746952,6-DifluorobenzonitrileHCID 5362487SulfurHCID 106795541-Bromo-3-methoxy-5-methylbenzeneHCID 178418400CID 53628100

生成物 1

HCID 105163882-Fluoro-6-[(3-methyl-5-methoxyphenyl)thio]benzonitrile

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒HCID 18522661Acetone cardice溶媒

実験手順

A solution of 1 g (0.005 mol) of 3-bromo-5-methoxytoluene in 10 mL of freshly distilled THF was cooled in dry ice/acetone and stirred under a N2 atmosphere. To this was added dropwise via a syringe 8.46 mL (0.011 mol) of sec-BuLi (1.3M in cyclohexane). The resultant mixture was stirred for 10 min after which 0.19 g of elemental sulfur was added in one portion. The reaction mixture was brought to room temperature and left stirring for 12 h. The mixture was cooled in ice/water bath. 0.69 g (0.005 mol) of 2,6-difluorobenzonitrile in 5 mL of dry DMSO was added. After sitting for 20 min, the mixture was poured into water (100 mL) and extracted with 3×50 mL of EtOAc. The EtOAc solution was washed with 1N NaOH, water, and dried over MgSO4Removal of EtOAc under vacuo resulted in a crude product which was chromatographed on silica gel (flash; EtOAc/Hexane 1:9). This resulted in 0.63 g (46%) of 2-fluoro-6-[(3-methyl-5-methoxyphenyl)thio]benzonitrile: mp 94°-95° C.; NMR (Me2SO-d6, 200 MHz) δ 2.28 (s, 3H), 3.7 (s, 3H), 6.8-7 (m, 4H), 7.34 (apparent d, 1H), 7.62 (dd, 1H). Anal. Calc. for C15H12NOSF: C, 65.92; H, 4.43; N, 5.12; S, 11.73. Found: C, 66.03; H, 4.49; N, 5.09; S, 11.8.

後処理

  1. additionwas added in one portion
  2. customwas brought to room temperature
  3. waitleft
  4. stirringstirring for 12 h
  5. extractionextracted with 3×50 mL of EtOAc
  6. washThe EtOAc solution was washed with 1N NaOH, water
  7. dry with materialdried over MgSO4Removal of EtOAc under vacuo
  8. customresulted in a crude product which
  9. customwas chromatographed on silica gel (flash; EtOAc/Hexane 1:9)
  10. customThis resulted in 0.63 g (46%) of 2-fluoro-6-[(3-methyl-5-methoxyphenyl)thio]benzonitrile

出典と根拠

ORDレコード
ord-6c9f5721435e410ba7c84870a32cbc44
出典データセット
uspto-grants-1998_03
特許番号
US05723452

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