Triphenylphosphine → 2,2,2-Trichloroethyl 2-[2-(aminomethyl)-4-chlorophenyl]azetidine-1-carboxylate

HRID 1058261ノート

反応式

HRID 1058261 の反応式
C1CCN2C(=[N:5]CCC2)CC1.[Cl:12][C:13]1[CH:18]=[CH:17][C:16]([CH:19]2[CH2:22][CH2:21][N:20]2[C:23]([O:25][CH2:26][C:27]([Cl:30])([Cl:29])[Cl:28])=[O:24])=[C:15]([CH2:31]O)[CH:14]=1.C1C=CC(P(N=[N+]=[N-])(C2C=CC=CC=2)=O)=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[OH-].[Na+]>C1COCC1.O.CO>[NH2:5][CH2:31][C:15]1[CH:14]=[C:13]([Cl:12])[CH:18]=[CH:17][C:16]=1[CH:19]1[CH2:22][CH2:21][N:20]1[C:23]([O:25][CH2:26][C:27]([Cl:30])([Cl:29])[Cl:28])=[O:24]

参加物

10

反応物 5

HCID 11776TriphenylphosphineHCID 14798Sodium HydroxideHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 199401P,P-Diphenylphosphinic azideHCID 186724042,2,2-Trichloroethyl 2-[4-chloro-2-(hydroxymethyl)phenyl]azetidine-1-carboxylate

生成物 1

HCID 186723262,2,2-Trichloroethyl 2-[2-(aminomethyl)-4-chlorophenyl]azetidine-1-carboxylate収率 79.7%

試薬・触媒・溶媒 4

HCID 962Water触媒HCID 887Methanol溶媒HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒2 回

実験手順

DBU (0.209 mL, 1.40 mmol) was added to a stirred solution of 2,2,2-trichloroethyl 2-[4-chloro-2-(hydroxymethyl)phenyl]azetidine-1-carboxylate (0.346 g, 0.927 mmol) and DPPA (0.302 mL, 1.40 mmol) in THF (2 mL) at 0° C. After 2 h the reaction was partitioned between ether and water and the organic layer was washed with 1 M sodium hydroxide solution (2 times) and 1 M HCl solution, dried (Na2SO4) and evaporated in vacuo to an oil. Triphenylphosphine (0.262 g, 1.00 mmol) was added to a stirred solution of this oil in THF (2 mL) and water (4 drops). After 16 h methanol (2 mL), water (1 mL) and sodium hydroxide (1 pellet) were added, the mixture was stirred for a further 15 min and then was partitioned between ether and water. The organic layer was extracted into dilute aqueous acetic acid which was basicified with sodium hydroxide and extracted with ether. This organic layer was dried (Na2SO4) and evaporated in vacuo to an oil which was purified by flash column chromatography on silica (eluting with a chloroform/10% ammonium hydroxide in methanol gradient, 1-4% ammonium hydroxide/methanol) to give 2,2,2-trichloroethyl 2-[2-(aminomethyl)-4-chlorophenyl]azetidine-1-carboxylate (275 mg) as an oil: 1H NMR (CDCl3, 400 MHz) δ 2.11 (m, 1H), 2.78 (m, 1H), 3.77 (br d, J=14.4 Hz, 1H), 3.87 (br d, J=14.4 Hz, 1H), 4.16 (br m, 2H), 4.64 (br m, 2H), 5.63 (br s, 1H), 7.27 (obscured m, 1H), 7.35 (s, 1H), 7.50 (br s, 1H).

後処理

  1. customAfter 2 h the reaction was partitioned between ether and water
  2. washthe organic layer was washed with 1 M sodium hydroxide solution (2 times) and 1 M HCl solution
  3. dry with materialdried (Na2SO4)
  4. customevaporated in vacuo to an oil
  5. customwas partitioned between ether and water
  6. extractionThe organic layer was extracted into dilute aqueous acetic acid which
  7. extractionextracted with ether
  8. dry with materialThis organic layer was dried (Na2SO4)
  9. customevaporated in vacuo to an oil which
  10. customwas purified by flash column chromatography on silica (
  11. washeluting with a chloroform/10% ammonium hydroxide in methanol gradient, 1-4% ammonium hydroxide/methanol)

出典と根拠

ORDレコード
ord-f12da4da33ea485993468b3b30686b55
出典データセット
uspto-grants-2003_02
特許番号
US06515011B2

反応ノート

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