Hydrochloric Acid → [(R)-2-(3-cyano-azetidin-1-yl)-1-cyclopropyl-2-oxo-ethyl]-carbamic acid tert-butyl ester

HRID 1898647노트

반응식

HRID 1898647 반응식
[C:1]([O:5][C:6]([NH:8][C@H:9]([CH:13]1[CH2:15][CH2:14]1)[C:10]([OH:12])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].F[B-](F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.Cl.[C:39]([CH:41]1[CH2:44][NH:43][CH2:42]1)#[N:40].C(N(CC)C(C)C)(C)C.Cl>ClCCl.O>[C:1]([O:5][C:6](=[O:7])[NH:8][C@H:9]([CH:13]1[CH2:15][CH2:14]1)[C:10]([N:43]1[CH2:44][CH:41]([C:39]#[N:40])[CH2:42]1)=[O:12])([CH3:2])([CH3:3])[CH3:4]

참가 물질

8

반응물 5

HCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 7146275(R)-2-((tert-Butoxycarbonyl)amino)-2-cyclopropylacetic acidHCID 45072465Azetidine-3-carbonitrile hydrochloride

생성물 1

HCID 67385839[(R)-2-(3-cyano-azetidin-1-yl)-1-cyclopropyl-2-oxo-ethyl]-carbamic acid tert-butyl ester수율 83.5%

시약·촉매·용매 2

HCID 962Water용매HCID 6344Dichloromethane용매2회

실험 절차

(R)-2-(tert-butoxycarbonylamino)-2-cyclopropylacetic acid (2.25 g, 10.5 mmol) and O-benzotriazol-1-yl-N,N,N′,N′-tetramethyluronium tetrafluoroborate (3.69 g, 11.5 mmol) were dissolved in dichloromethane (105 mL). 3-Cyanoazetidine hydrochloride (1.36 g, 11.5 mmol) and then N,N-diisopropylethylamine (4.5 mL, 26.1 mmol) were added and the mixture was stirred at room temperature for 5 h. Water, dilute HCl and more dichloromethane were added, the layers were separated and the aqueous layer was extracted once more with dichloromethane. The combined organic layers were washed with sodium chloride solution, dried over sodium sulfate and concentrated. The residue was purified by silica gel chromatography (methanol/dichloromethane) to give 2.45 g (83%) of [(R)-2-(3-cyano-azetidin-1-yl)-1-cyclopropyl-2-oxo-ethyl]-carbamic acid tert-butyl ester.

후처리

  1. customthe layers were separated
  2. extractionthe aqueous layer was extracted once more with dichloromethane
  3. washThe combined organic layers were washed with sodium chloride solution
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated
  6. customThe residue was purified by silica gel chromatography (methanol/dichloromethane)

출처 및 근거

ORD 기록
ord-0bd8351d38d6410ea14c90a426e600a6
출처 데이터셋
uspto-grants-2013_08
특허 번호
US08518945B2

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