Hydrochloric Acid → Tert-butyl 4-oxo-octahydropiperazino[2,1-c]morpholine-8-carboxylate

HRID 2063311ノート

反応式

HRID 2063311 の反応式
[OH:1][CH2:2][CH:3]1[NH:8][CH2:7][CH2:6][N:5]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:4]1.C(N(CC)CC)C.Cl[CH2:24][C:25](Cl)=[O:26].OS([O-])(=O)=O.[K+].[H-].[Na+].Cl.[OH-].[Na+]>C(Cl)Cl.CN(C=O)C.C(OCC)(=O)C>[O:26]=[C:25]1[CH2:24][O:1][CH2:2][CH:3]2[CH2:4][N:5]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:6][CH2:7][N:8]12

参加物

11

反応物 7

HCID 313Hydrochloric AcidHCID 6577Chloroacetyl chlorideHCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 24758Sodium hydrideHCID 516920Potassium bisulfateHCID 223865084-N-Boc-2-hydroxymethylpiperazine

生成物 1

HCID 16123288Tert-butyl 4-oxo-octahydropiperazino[2,1-c]morpholine-8-carboxylate収率 21%

試薬・触媒・溶媒 3

HCID 6228Dimethylformamide溶媒HCID 6344Dichloromethane溶媒2 回HCID 8857Ethyl Acetate溶媒

反応条件

温度
0 °C

実験手順

To a solution of tert-butyl 3-(hydroxymethyl)piperazine-1-carboxylate (360 mg, 1.7 mmol) in methylene chloride (10 mL) was added triethylamine (505 mg, 5.0 mmol) at 0° C. Chloroacetyl chloride (282 mg, 2.5 mmol) was dissolved in methylene chloride (5 mL) and the solution was added to the former solution drop by drop at 0° C. The reaction mixture was stirred at 0° C. for 1 h and then at RT for 3 h. An aqueous solution of KHSO4 (1M, 5 mL) was added and then the organic phase was separated by means of a phase separator column. The solvent was removed by evaporation and the amide intermediate, which was purified by silica gel chromatography, was dissolved in DMF (2 mL). While cooling and under nitrogen the solution was added drop wise to a suspension of NaH (60 mg, 2.5 mmol) in DMF. The mixture was stirred at RT for 48 h, then diluted with ethyl acetate and then pored over aqueous HCl (0.5 M). The pH was adjusted to 12 with NaOH and then the organic phase was separated. The solvent was removed by evaporation and the product was purified by silica gel chromatography. There was obtained 90 mg (21%) of tert-butyl 4-oxohexahydropyrazino[2,1-c][1,4]oxazine-8(1H)-carboxylate. 1H NMR (500 MHz, CDCl3): 1.4 (s, 9H), 2.5-2.7 (m, 2H), 2.8 (m, 1H), 3.4-3.5 (m, 2H), 3.9-4.2 (m, 5H), 4.5 (d, 1H); LCMS: m/z 257 (M+1)+.

後処理

  1. additionthe solution was added to the former solution drop by drop at 0° C
  2. waitat RT for 3 h
  3. customthe organic phase was separated by means of a phase separator column
  4. customThe solvent was removed by evaporation
  5. customthe amide intermediate, which was purified by silica gel chromatography
  6. dissolutionwas dissolved in DMF (2 mL)
  7. temperatureWhile cooling and under nitrogen the solution
  8. additionwas added drop
  9. stirringThe mixture was stirred at RT for 48 h
  10. customthe organic phase was separated
  11. customThe solvent was removed by evaporation
  12. customthe product was purified by silica gel chromatography

出典と根拠

ORDレコード
ord-4be2187cd92c4363befbc41d01080f0d
出典データセット
uspto-grants-2012_10
特許番号
US08288370B2

反応ノート

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