2-Chloromethyl 2-(trimethylsilyl)ethyl ether → (S)-5-Biphenyl-4-ylmethyl-1-(2-trimethylsilanylethoxymethyl)pyrrolidin-2-one

HRID 1641655ノート

反応式

HRID 1641655 の反応式
[C:1]1([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH:6]=[CH:5][C:4]([CH2:7][C@H:8]2[NH:12][C:11](=[O:13])[CH2:10][CH2:9]2)=[CH:3][CH:2]=1.C([Li])CCC.Cl[CH2:26][O:27][CH2:28][CH2:29][Si:30]([CH3:33])([CH3:32])[CH3:31]>C1COCC1.CCCCCC>[C:1]1([C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=2)[CH:2]=[CH:3][C:4]([CH2:7][C@H:8]2[N:12]([CH2:26][O:27][CH2:28][CH2:29][Si:30]([CH3:33])([CH3:32])[CH3:31])[C:11](=[O:13])[CH2:10][CH2:9]2)=[CH:5][CH:6]=1

参加物

6

反応物 3

HCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl etherHCID 58160438(S)-5-[(Biphenyl-4-yl)methyl]pyrrolidin-2-oneHCID 178418339Butyllithium

生成物 1

HCID 59318461(S)-5-Biphenyl-4-ylmethyl-1-(2-trimethylsilanylethoxymethyl)pyrrolidin-2-one

試薬・触媒・溶媒 2

HCID 8028Tetrahydrofuran溶媒HCID 8058Hexane溶媒

反応条件

温度
-78 °C

実験手順

804 mg (3.2 mmol) (S)-5-biphenyl-4-ylmethylpyrrolidin-2-one (1-a, R1=H) is dissolved in 16 ml dry THF and cooled to −78° C. After the addition of 2.21 ml butyl lithium in hexane (1.59 M), the yellow solution is stirred at −78° C. for 30 min. Subsequently, 680 μl (640 mg=3.84 mmol) (2-chloromethoxyethyl)-trimethylsilane (SEM-Cl) is added and stirring is continued at −20° C. for 5 h. The mixture is then allowed to warm up to room temperature overnight. The reaction is then quenched by addition of 10 ml saturated NH4Cl solution followed by 10 ml water and extracted with 2×40 ml isopropyl acetate. The layers are separated and the organic layer dried over MgSO4, filtered and evaporated. The resulting residue (1.33 g) is purified using column chromatography (dichloromethane:triethylamine=99.5:0.5→dichloromethane:methanol:triethylamine=98.5:1:0.5) to give (S)-5-Biphenyl-4-ylmethyl-1-(2-trimethylsilanylethoxymethyl)pyrrolidin-2-one (1-a, R1=SEM) as a yellow oil. NMR (400 MHz, CDCl3, δ/ppm): 7.58 (m, 4 H); 7.47 (m, 2 H); 7.37 (m, 1 H); 7.30 (m, 2 H); 5.04 (d, J=10.6, 1 H); 4.70 (d, J=10.6, 1 H); 4.03 (m, 1 H); 3.59 (m, 2 H); 3.24 (dd, J=4.2, 13.4, 1 H); 2.67 (dd, J=9.1, 13.4, 1 H); 2.33 (t, J=8.2, 2 H); 2.10 (m, 1H); 1.81 (m, 1 H); 1.00 (m, 2 H); 0.06 (s, 9 H). MS (ESI, m/e) 382 [M+H]+; 763 [2M+H]+. IR (solution in CH2Cl2, ν/cm−1): 3057; 2951; 1702; 1487; 1414; 1249; 1073; 859; 836; 759; 697.

後処理

  1. stirringstirring
  2. waitis continued at −20° C. for 5 h
  3. temperatureto warm up to room temperature overnight
  4. customThe reaction is then quenched by addition of 10 ml saturated NH4Cl solution
  5. extractionextracted with 2×40 ml isopropyl acetate
  6. customThe layers are separated
  7. dry with materialthe organic layer dried over MgSO4
  8. filtrationfiltered
  9. customevaporated
  10. customThe resulting residue (1.33 g) is purified

出典と根拠

ORDレコード
ord-f5ad409b6dd04805a15e4bcf6db21273
出典データセット
uspto-grants-2012_02
特許番号
US08115016B2

反応ノート

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