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

HRID 1481732노트

반응식

HRID 1481732 반응식
[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

참가 물질

7

반응물 4

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

생성물 1

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

시약·촉매·용매 2

HCID 962Water용매HCID 13387N-methyl-2-pyrrolidone용매

반응 조건

온도
780 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-dfaf359b17dc4ddeab2026575f785e5a
출처 데이터셋
uspto-grants-2016_08
특허 번호
US09409905B2

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