Iodine → Tert-butyl (2-chloro-3-iodopyridin-4-YL)carbamate

HRID 1432950

反応式

HRID 1432950 の反応式
C([Li])(C)(C)C.[C:6]([O:10][C:11](=[O:20])[NH:12][C:13]1[CH:18]=[CH:17][N:16]=[C:15]([Cl:19])[CH:14]=1)([CH3:9])([CH3:8])[CH3:7].[I:21]I>C1COCC1>[C:6]([O:10][C:11](=[O:20])[NH:12][C:13]1[CH:18]=[CH:17][N:16]=[C:15]([Cl:19])[C:14]=1[I:21])([CH3:9])([CH3:7])[CH3:8]

参加物

5

反応物 3

HCID 807IodineHCID 21858447tert-butyl N-(2-chloropyridin-4-yl)carbamateHCID 178418306HCID 178418306、化合物

生成物 1

HCID 44721300Tert-butyl (2-chloro-3-iodopyridin-4-YL)carbamate収率 85.9%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
-78 °C

実験手順

tert-Butyllithium (36.3 mL, 1.7M in pentane) is added dropwise to a solution of (2-chloro-pyridin-4-yl)-carbamic acid tert-butyl ester (6.00 g, 26.2 mmol) in THF (46 mL) at −78° C. under Ar. The yellow/orange mixture is stirred for 2 h at −78° C. then warmed to −40° C. for 1 h then cooled to −78° C. before dropwise addition of I2 (15.65 g, 61.7 mmol) in THF (49 mL). The reaction mixture is stirred for 1.5 h at −78° C. then at −10° C. for 30 minutes. The reaction is quenched with saturated NH4Cl solution then diluted with CH2Cl2 and washed with saturated NH4Cl, saturated sodium thiosulfate, water then brine. The organic layer is dried over MgSO4, filtered and concentrated to dryness. The crude product is chromatographed eluting with 1-2% MeOH/CH2Cl2 to yield the title product (7.96 g, 22.5 mmol) as a bright yellow solid. 1H NMR (CDCl3, 300 MHz) δ8.14 (d, 1H), 8.02 (d, 1H), 7.32 (bs, 1H), 1.60 (s, 9H). EI MS [M]+=354, 356, Cl pattern.

後処理

  1. temperaturethen warmed to −40° C. for 1 h
  2. stirringThe reaction mixture is stirred for 1.5 h at −78° C.
  3. waitat −10° C. for 30 minutes
  4. customThe reaction is quenched with saturated NH4Cl solution
  5. additionthen diluted with CH2Cl2
  6. washwashed with saturated NH4Cl, saturated sodium thiosulfate, water
  7. dry with materialThe organic layer is dried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated to dryness
  10. customThe crude product is chromatographed
  11. washeluting with 1-2% MeOH/CH2Cl2

出典と根拠

ORDレコード
ord-83fc020bb3b84962a65c34a03a627800
出典データセット
uspto-grants-2009_11
特許番号
US07612075B2

関連ノート

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