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

HRID 1898647ノート

反応式

HRID 1898647 の反応式
[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]

参加物

8

反応物 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

生成物 1

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

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6344Dichloromethane溶媒2 回

実験手順

(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.

後処理

  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)

出典と根拠

ORDレコード
ord-0bd8351d38d6410ea14c90a426e600a6
出典データセット
uspto-grants-2013_08
特許番号
US08518945B2

反応ノート

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