Hydrochloric Acid → tert-butyl 3-(5-bromo-1-methyl-1H-indol-2-yl)pyrrolidine-1-carboxylate

HRID 1481732ノート

反応式

HRID 1481732 の反応式
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([Br:8])=[CH:4][C:3]=1[C:9]#[C:10][CH:11]1[CH2:15][CH2:14][N:13]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:12]1.[CH3:23]C([O-])(C)C.[K+].CI.Cl>CN1C(=O)CCC1.O>[Br:8][C:5]1[CH:4]=[C:3]2[C:2](=[CH:7][CH:6]=1)[N:1]([CH3:23])[C:10]([CH:11]1[CH2:15][CH2:14][N:13]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:12]1)=[CH:9]2

参加物

7

反応物 4

HCID 313Hydrochloric AcidHCID 6328Methyl iodideHCID 23665647Potassium tert-butoxideHCID 89421756Tert-butyl 3-((2-amino-5-bromophenyl)ethynyl)pyrrolidine-1-carboxylate

生成物 1

HCID 71284358tert-butyl 3-(5-bromo-1-methyl-1H-indol-2-yl)pyrrolidine-1-carboxylate収率 87.5%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 13387N-methyl-2-pyrrolidone溶媒

反応条件

温度
780 °C

実験手順

To degassed with argon solution of tert-butyl 3-((2-amino-5-bromophenyl)ethynyl)pyrrolidine-1-carboxylate (5.69 g, 15.58 mmol) in NMP (30 mL) was added t-BuOK (3.9 g, 34.75 mmol). Mixture was heated at 780° C. for 45 min before it was cooled to 0° C. in an ice-bath. MeI (3.0 mL, 48.08 mmol) was added dropwise and reaction was allowed to warm to room temperature and stirred 30 min. Then reaction was diluted with H2O (100 mL) and acidified with 1M aqueous HCl to pH˜2. Product was extracted with EtOAc (3×150 mL). Combined organics were washed with NaCl (aqueous saturated) and dried over Na2SO4. Upon solvent removal residue was purified by column chromatography using EtOAc/hexanes (gradient 0-40%) to afford tert-butyl 3-(5-bromo-1-methyl-1H-indol-2-yl)pyrrolidine-1-carboxylate (5.17 g) in 87% yield.

後処理

  1. temperaturewas cooled to 0° C. in an ice-bath
  2. customreaction
  3. temperatureto warm to room temperature
  4. customThen reaction
  5. extractionProduct was extracted with EtOAc (3×150 mL)
  6. washCombined organics were washed with NaCl (aqueous saturated)
  7. dry with materialdried over Na2SO4
  8. customUpon solvent removal residue
  9. customwas purified by column chromatography

出典と根拠

ORDレコード
ord-dfaf359b17dc4ddeab2026575f785e5a
出典データセット
uspto-grants-2016_08
特許番号
US09409905B2

反応ノート

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