Imidazole → Tert-butyl 4-iodopiperidine-1-carboxylate

HRID 454894

반응식

HRID 454894 반응식
O[CH:2]1[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:4][CH2:3]1.N1C=CN=C1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[I:39]I>C1COCC1.C(OCC)(=O)C.[Cl-].[Na+].O.O>[I:39][CH:2]1[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:4][CH2:3]1

참가 물질

9

반응물 4

HCID 795ImidazoleHCID 807IodineHCID 11776TriphenylphosphineHCID 643502Tert-butyl 4-hydroxypiperidine-1-carboxylate

생성물 1

HCID 10892302Tert-butyl 4-iodopiperidine-1-carboxylate수율 83.8%

시약·촉매·용매 4

HCID 962Water용매HCID 8028Tetrahydrofuran용매2회HCID 8857Ethyl Acetate용매HCID 57417360Sodium chloride; water용매

실험 절차

A solution of tert-butyl 4-hydroxypiperidine-1-carboxylate (246 g, 1.224 mol), imidazole (100 g, 1.469 mol, 1.2 eq.) and triphenylphosphine (385 g, 1.469 mol, 1.2 eq.) in THF (750 mL) was cooled using an ice bath. Then a solution of iodine (373 g, 1.469 mol, 1.2 eq.) in THF (750 mL) was added slowly over a period of 1 hour while keeping the internal temperature below 18° C. The resulting mixture was allowed to stir at room temperature for 5 hours and the mixture was diluted with ethyl acetate (2 L), brine (1 L) and water (500 mL). The organic layer was separated and the aqueous layer was extracted with ethyl acetate (1 L×2). The organic layers were combined, washed with 15% aqueous sodium sulfite (1 L), brine (1 L), dried and concentrated. The resulting residue was stirred with hexanes (2 L) and the solid was removed by filtration. The solid was stirred with hexanes (2 L×2) and filtered. The filtrate was concentrated to give 363 g of crude oil which was purified by column chromatography (eluting with hexanes/ethyl acetate=50:1 to 20:1) to afford 319 g of tert-butyl 4-iodopiperidine-1-carboxylate.

후처리

  1. customthe internal temperature below 18° C
  2. customThe organic layer was separated
  3. extractionthe aqueous layer was extracted with ethyl acetate (1 L×2)
  4. washwashed with 15% aqueous sodium sulfite (1 L), brine (1 L)
  5. customdried
  6. concentrationconcentrated
  7. stirringThe resulting residue was stirred with hexanes (2 L)
  8. customthe solid was removed by filtration
  9. stirringThe solid was stirred with hexanes (2 L×2)
  10. filtrationfiltered
  11. concentrationThe filtrate was concentrated
  12. customto give 363 g of crude oil which
  13. customwas purified by column chromatography (eluting with hexanes/ethyl acetate=50:1 to 20:1)

출처 및 근거

ORD 기록
ord-11c133c073634a19b717441ee4e4c6c5
출처 데이터셋
uspto-grants-2013_07
특허 번호
US08497265B2

연결된 노트

불러오는 중…