N-(2-Bromo-5-chloro-pyridin-3-yl)-4-chloro-N-methoxvmethyl-3-trifluoromethyl-benzenesulfonamide → 8-({5-Chloro-3-[(4-chloro-3-trifluoromethyl-benzenesulfonyl)-methoxymethyl-amino]-pyridin-2-yl}-hydroxy-methyl)-2,3-dihydro-benzo[1,4]oxazine-4-carboxylic acid tert-butyl ester

HRID 419163ノート

反応式

HRID 419163 の反応式
Br[C:2]1[C:7]([N:8]([CH2:23][O:24][CH3:25])[S:9]([C:12]2[CH:17]=[CH:16][C:15]([Cl:18])=[C:14]([C:19]([F:22])([F:21])[F:20])[CH:13]=2)(=[O:11])=[O:10])=[CH:6][C:5]([Cl:26])=[CH:4][N:3]=1.C([Mg]Cl)(C)C.[C:32]([O:36][C:37]([N:39]1[C:44]2[CH:45]=[CH:46][CH:47]=[C:48]([CH:49]=[O:50])[C:43]=2[O:42][CH2:41][CH2:40]1)=[O:38])([CH3:35])([CH3:34])[CH3:33]>C1COCC1>[C:32]([O:36][C:37]([N:39]1[C:44]2[CH:45]=[CH:46][CH:47]=[C:48]([CH:49]([C:2]3[C:7]([N:8]([S:9]([C:12]4[CH:17]=[CH:16][C:15]([Cl:18])=[C:14]([C:19]([F:22])([F:21])[F:20])[CH:13]=4)(=[O:11])=[O:10])[CH2:23][O:24][CH3:25])=[CH:6][C:5]([Cl:26])=[CH:4][N:3]=3)[OH:50])[C:43]=2[O:42][CH2:41][CH2:40]1)=[O:38])([CH3:35])([CH3:33])[CH3:34]

参加物

5

反応物 3

HCID 57942086N-(2-Bromo-5-chloro-pyridin-3-yl)-4-chloro-N-methoxvmethyl-3-trifluoromethyl-benzenesulfonamideHCID 57942605Tert-butyl 8-formyl-2,3-dihydro-4H-benzo[B][1,4]oxazine-4-carboxylateHCID 178418918HCID 178418918、化合物

生成物 1

HCID 666489408-({5-Chloro-3-[(4-chloro-3-trifluoromethyl-benzenesulfonyl)-methoxymethyl-amino]-pyridin-2-yl}-hydroxy-methyl)-2,3-dihydro-benzo[1,4]oxazine-4-carboxylic acid tert-butyl ester収率 56.5%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
0 °C

実験手順

To a solution of N-(2-bromo-5-chloro-pyridin-3-yl)-4-chloro-N-methoxymethyl-3-trifluoromethyl-benzenesulfonamide (2.92 g, 6.18 mmol) in THF (12 mL) under nitrogen atmosphere at −20° C. was added isopropylmagnesium chloride (2 M solution in THF, 6.5 mL, 13.0 mmol) via dropwise addition. The mixture was then stirred for 1 hour at 0° C. followed by the addition of a solution of 8-formyl-2,3-dihydro-benzo[1,4]oxazine-4-carboxylic acid tert-butyl ester (273.5 mg, 1.54 mmol) in THF (2 mL) at −20° C. The mixture was stirred at room temperature overnight, quenched with saturated aqueous NH4Cl solution (5 mL), and extracted with EtOAc (2×200 mL). The combined organic extracts were washed with saturated aqueous NH4Cl solution (40 mL) and brine (40 mL), dried (Na2SO4), and concentrated under reduced pressure. The obtained residue was purified by flash column chromatography on silica gel (10% EtOAc-hexanes to 90% EtOAc-hexanes) to obtain 8-({5-chloro-3-[(4-chloro-3-trifluoromethyl-benzenesulfonyl)-methoxymethyl-amino]-pyridin-2-yl}-hydroxy-methyl)-2,3-dihydro-benzo[1,4]oxazine-4-carboxylic acid tert-butyl ester (590.2 mg) as yellow syrup. MS m/z: 678.0 (M+H)+.

後処理

  1. additionvia dropwise addition
  2. stirringThe mixture was stirred at room temperature overnight
  3. customquenched with saturated aqueous NH4Cl solution (5 mL)
  4. extractionextracted with EtOAc (2×200 mL)
  5. washThe combined organic extracts were washed with saturated aqueous NH4Cl solution (40 mL) and brine (40 mL)
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated under reduced pressure
  8. customThe obtained residue was purified by flash column chromatography on silica gel (10% EtOAc-hexanes to 90% EtOAc-hexanes)

出典と根拠

ORDレコード
ord-4dd857d1142b4368862cadb8743c2663
出典データセット
uspto-grants-2012_01
特許番号
US08093247B2

反応ノート

読み込み中…