4-Methylmorpholine → 1-Benzyl-pyrrolidine-2-carboxylic acid (2,2-dimethoxy-ethyl)-amide

HRID 1869229ノート

反応式

HRID 1869229 の反応式
[CH2:1]([N:8]1[CH2:12][CH2:11][CH2:10][CH:9]1[C:13]([OH:15])=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:16][O:17][CH:18]([O:21][CH3:22])[CH2:19][NH2:20].CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1.CN1CCOCC1.C([O-])(O)=O.[Na+]>C(Cl)Cl>[CH3:16][O:17][CH:18]([O:21][CH3:22])[CH2:19][NH:20][C:13]([CH:9]1[CH2:10][CH2:11][CH2:12][N:8]1[CH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)=[O:15]

参加物

8

反応物 6

HCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 89728Aminoacetaldehyde dimethyl acetalHCID 516892Sodium BicarbonateHCID 562952N-Benzyl-DL-prolineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride

生成物 1

HCID 574884281-Benzyl-pyrrolidine-2-carboxylic acid (2,2-dimethoxy-ethyl)-amide

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

反応条件

温度
25 °C

実験手順

To 1-Benzyl-pyrrolidine-2-carboxylic acid (474) (Belokon, Y. N. at al; Tetrahedron Asymmetry 1998, 9, 4249-4252) in CH2Cl2 (20 mL) was added 2,2-dimethoxy-ethylamine (614 mg, 5.84 mmol), EDCl (1.12 g, 5.84 mmol), HOBT (658 mg, 4.87 mmol), and NMM (1.08 mL, 9.8 mmol). The reaction mixture was stirred overnight at 25° C. Saturated aqueous NaHCO3 solution (50 mL) was added. The aqueous layer was extracted with CH2Cl2 (50 mL×3). The combined organic layers was washed with brine (50 mL), dried over Na2SO4, and concentrated by rotary evaporator to give 1-benzyl-pyrrolidine-2-carboxylic acid (2,2-dimethoxy-ethyl)-amide as yellow oil. To 1-benzyl-pyrrolidine-2-carboxylic acid (2,2-dimethoxy-ethyl)-amide was added acetic acid (10 mL) and ammonium acetate (11 g). The reaction mixture was heated to 140° C. overnight. After it was cooled down, it was poured into 100 mL ice-water with stirring. Solid NaHCO3 was added in small portion with stirring to adjust the pH of the solution to 8-9. The aqueous solution was extracted with EtOAc (100 mL×2). The combined organic layers was washed with brine, dried over Na2SO4, and concentrated with rotary evaporator. Compound 475 (110 mg) was isolated by SiO2 chromatography (CH2Cl2/MeOH/NH3: 40:1:0.1 to 20:1:0.1). MS: m/z 228.3 [M+H]+.

後処理

  1. extractionThe aqueous layer was extracted with CH2Cl2 (50 mL×3)
  2. washThe combined organic layers was washed with brine (50 mL)
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated by rotary evaporator

出典と根拠

ORDレコード
ord-2f67e9784515497c8e97e282dd261897
出典データセット
uspto-grants-2009_12
特許番号
US07638513B2

反応ノート

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