Chloride → 1-(2-(Isochroman-1-yl)ethyl)-piperazine

HRID 368878

반응식

HRID 368878 반응식
[Cl-].[CH:2]1([CH2:12][CH2:13]O)[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH2:5][CH2:4][O:3]1.C(N(C(C)C)CC)(C)C.Cl.[NH:25]1[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]1>O1CCCC1.N1C=CC=CC=1>[CH:2]1([CH2:12][CH2:13][N:25]2[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]2)[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH2:5][CH2:4][O:3]1

참가 물질

8

반응물 5

HCID 312ChlorideHCID 313Hydrochloric AcidHCID 4837PiperazineHCID 81531DiisopropylethylamineHCID 14141298(-)-2-(Isochroman-1-yl)ethanol

생성물 1

HCID 232888881-(2-(Isochroman-1-yl)ethyl)-piperazine수율 99.9%

시약·촉매·용매 2

HCID 1049Pyridine용매HCID 8028Tetrahydrofuran용매

실험 절차

Methanesulfony chloride (524 ml, 6.77 mol) is added to a cooled mixture of (-)-2-(isochroman-1-yl)ethanol (EXAMPLE 48, LXXIX, 940 g, 5.2 mol), diisopropylethylamine (1.27 l, 7.29 mol) in tetrahydrofuran (5.6 l). After 4 hr, aqueous hydrochloric acid (1N, 8 l) is added and the mixture extracted with ethyl acetate (17 l). The organic phase is washed with saturated aqueous sodium chloride (2 l) and concentrated under reduced pressure. The concentrate is dissolved in pyridine (4 l) and added to a mixture of piperazine (2.71 kg, 31.5 mol) in pyridine (6.88 l). After 21 hr, the mixture is concentrated under reduced pressure to a slurry and the solids filtered off and washed with ethyl acetate (10 l). The filtrate is concentrated under reduced pressure to an oil and azeotroped with heptane (8 l). The oil is dissolved in ethyl acetate (20 l) and washed with saturated aqueous sodium bicarbonate (2.4 l). The organic phase is concentrated under reduced pressure and the oil azeotroped with toluene (4 l) to give 1.28 kg of the title compound; HPLC retention time=7.3 min (Column=Zorbax C-8; Injection vol.=10 μl; Mobile phase=water (1100 ml)/acetonitrile (500 ml)/methanol (400 mm)/potassium phosphate, monobasic (15 g); Detector=254 nm; Flow rate =0.5 ml/min).

후처리

  1. extractionthe mixture extracted with ethyl acetate (17 l)
  2. washThe organic phase is washed with saturated aqueous sodium chloride (2 l)
  3. concentrationconcentrated under reduced pressure
  4. dissolutionThe concentrate is dissolved in pyridine (4 l)
  5. waitAfter 21 hr
  6. concentrationthe mixture is concentrated under reduced pressure to a slurry
  7. filtrationthe solids filtered off
  8. washwashed with ethyl acetate (10 l)
  9. concentrationThe filtrate is concentrated under reduced pressure to an oil
  10. customazeotroped with heptane (8 l)
  11. dissolutionThe oil is dissolved in ethyl acetate (20 l)
  12. washwashed with saturated aqueous sodium bicarbonate (2.4 l)
  13. concentrationThe organic phase is concentrated under reduced pressure
  14. customthe oil azeotroped with toluene (4 l)

출처 및 근거

ORD 기록
ord-6f5567adcd224b6a9af10c3fb37303ff
출처 데이터셋
uspto-grants-2000_10
특허 번호
US06133446

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