Azetidine → tert-Butyl [(2S)-1-(azetidin-1-yl)-3-methyl-1-oxobutan-2-yl]carbamate

HRID 1808775ノート

反応式

HRID 1808775 の反応式
[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH:13]([CH3:15])[CH3:14])[C:10]([OH:12])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].CCN=C=NC[CH2:22][CH2:23][N:24]([CH3:26])C.Cl.ON1C(=O)CCC1=O.CCN(C(C)C)C(C)C.N1CCC1>C(Cl)Cl>[N:24]1([C:10](=[O:12])[C@@H:9]([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:2])([CH3:3])[CH3:4])[CH:13]([CH3:15])[CH3:14])[CH2:23][CH2:22][CH2:26]1

参加物

7

反応物 5

HCID 10422AzetidineHCID 80170N-HydroxysuccinimideHCID 81531DiisopropylethylamineHCID 83693Boc-L-ValineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride

生成物 1

HCID 52180842tert-Butyl [(2S)-1-(azetidin-1-yl)-3-methyl-1-oxobutan-2-yl]carbamate収率 71.2%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

反応条件

温度
0 °C

実験手順

(S)-2-(Tert-butoxycarbonylamino)-3-methylbutanoic acid (50.0 g, 230.1 mmol), EDC hydrochloride (52.9 g, 276.2 mmol) and 1-hydroxypyrrolidine-2,5-dione (39.7 g, 345.2 mmol) was mixed in DCM (180 mL). The mixture was cooled to 0° C. and DIPEA (160 mL, 920.6 mmol) was added. After 1 h at 0° C. was azetidine (18.62 mL, 276.2 mmol) added. The resultant mixture was stirred at rt over night. The mixture was concentrated and the residue dissolved in DCM (200 mL). The organic phase was washed with NaHCO3 (saturated, 2×150 mL), HCl (1M aq. solution, 2×200 mL) and brine (150 mL), filtered through a phase separator and concentrated under reduced pressure to give the title compound (42 g, 71%). The obtained crude product was used without further purification.

後処理

  1. concentrationThe mixture was concentrated
  2. dissolutionthe residue dissolved in DCM (200 mL)
  3. washThe organic phase was washed with NaHCO3 (saturated, 2×150 mL), HCl (1M aq. solution, 2×200 mL) and brine (150 mL)
  4. filtrationfiltered through a phase separator
  5. concentrationconcentrated under reduced pressure

出典と根拠

ORDレコード
ord-47e54f0389574643b9bd888d46e5d6e3
出典データセット
uspto-grants-2013_01
特許番号
US08361998B2

反応ノート

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