Methanesulfonyl chloride → Methyl (3-bromo-5-fluorophenyl){1-[(S)-(4-chlorophenyl)(3-cyanophenyl)methyl]azetidin-3-ylidene}acetate

HRID 603008ノート

反応式

HRID 603008 の反応式
[Br:1][C:2]1[CH:3]=[C:4]([CH2:9][C:10]([O:12][CH3:13])=[O:11])[CH:5]=[C:6]([F:8])[CH:7]=1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[Cl:24][C:25]1[CH:30]=[CH:29][C:28]([C@H:31]([N:40]2[CH2:43][C:42](=O)[CH2:41]2)[C:32]2[CH:33]=[C:34]([CH:37]=[CH:38][CH:39]=2)[C:35]#[N:36])=[CH:27][CH:26]=1.CS(Cl)(=O)=O>C1COCC1.CN(C1C=CN=CC=1)C.O.CCOCC>[Br:1][C:2]1[CH:3]=[C:4]([C:9](=[C:42]2[CH2:43][N:40]([C@@H:31]([C:28]3[CH:27]=[CH:26][C:25]([Cl:24])=[CH:30][CH:29]=3)[C:32]3[CH:39]=[CH:38][CH:37]=[C:34]([C:35]#[N:36])[CH:33]=3)[CH2:41]2)[C:10]([O:12][CH3:13])=[O:11])[CH:5]=[C:6]([F:8])[CH:7]=1

参加物

9

反応物 4

HCID 31297Methanesulfonyl chlorideHCID 2733832Lithium HexamethyldisilazideHCID 59290393Methyl 2-(3-bromo-5-fluorophenyl)acetateHCID 670554063-[(S)-(4-chlorophenyl)(3-oxoazetidin-1-yl)methyl]benzonitrile

生成物 1

HCID 67055366Methyl (3-bromo-5-fluorophenyl){1-[(S)-(4-chlorophenyl)(3-cyanophenyl)methyl]azetidin-3-ylidene}acetate

試薬・触媒・溶媒 4

HCID 142844-(Dimethylamino)pyridine触媒HCID 962Water溶媒HCID 3283Diethyl Ether溶媒HCID 8028Tetrahydrofuran溶媒2 回

実験手順

To a solution of 14.55 g (58.87 mmol) of methyl (3-bromo-5-fluorophenyl)acetate in 200 mL of THF at −78° C., was added a solution of 56.80 mL (56.80 mmol) (1M in THF) of LHMDS. After the reaction mixture was stirred for 30 min., a solution of 15.60 g (52.57 mmol) of 3-[(S)-(4-chlorophenyl)(3-oxoazetidin-1-yl)methyl]benzonitrile in 50 mL of THF was added and the mixture was stirred for 2.5 h at −78° C. Then 8.35 g (68.33 mmol) of DMAP, 14.65 mL (84.09 mmol) of DEA, and 8.72 mL (110.38 mmol) of methanesulfonyl chloride were added, and the mixture was stirred for 1 h at −78° C. The mixture was then allowed to warm to rt and was stirred at rt for 12 h. The mixture was poured into 300 mL of ether and 100 mL of water. The water layer was extracted with ether (100 mL×2). The combined organic layer was dried over Na2S04 and concentrated. The residue was purified by silica gel chromatography with hexanes/ethyl acetate to afford the title compound as a white solid; 1H-NMR(CDCl3) δ 3.75(s, 3H), 3.87(s, 2H), 4.23-4.29(m, 2H), 4.59(s, 1H), 6.92 (d, 1H, J=12 Hz), 7.18(s, 1H), 7.20 (d, 1H, J=12 Hz), 7.31-7.38 (dd, 4H, J J11=28.4 Hz, J2=8.5 Hz), 7.42 (t, 1H, J=7.7 Hz), 7.54 (d, 1H, J=7.6 Hz), 7.66 (d, 1H, J=7.6 Hz), 7.76 (s, 1H); Mass Spectrum: m/e=525, (M+1, 35Cl79Br), 527 (M+1, 37Cl79Br/35Cl81Br), 529 (M+1, 37Cl81Br).

後処理

  1. stirringthe mixture was stirred for 2.5 h at −78° C
  2. stirringthe mixture was stirred for 1 h at −78° C
  3. stirringwas stirred at rt for 12 h
  4. extractionThe water layer was extracted with ether (100 mL×2)
  5. customThe combined organic layer was dried over Na2S04
  6. concentrationconcentrated
  7. customThe residue was purified by silica gel chromatography with hexanes/ethyl acetate

出典と根拠

ORDレコード
ord-b2ed4b37e6fb447293f6744521db27c5
出典データセット
uspto-grants-2011_03
特許番号
US07906652B2

反応ノート

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