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

HRID 454894

反応式

HRID 454894 の反応式
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

参加物

9

反応物 4

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

生成物 1

HCID 10892302Tert-butyl 4-iodopiperidine-1-carboxylate収率 83.8%

試薬・触媒・溶媒 4

HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒2 回HCID 8857Ethyl Acetate溶媒HCID 57417360Sodium chloride; water溶媒

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-11c133c073634a19b717441ee4e4c6c5
出典データセット
uspto-grants-2013_07
特許番号
US08497265B2

関連ノート

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