Cyanide → tert-Butyl 1-(4-cyanobenzyl)azetidine-3-carboxylate

HRID 1951923ノート

反応式

HRID 1951923 の反応式
C(O)(=O)C.[NH:5]1[CH2:8][CH:7]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:6]1.[CH:16]([C:18]1[CH:25]=[CH:24][C:21]([C:22]#[N:23])=[CH:20][CH:19]=1)=O.C([BH3-])#N.[Na+].[C-]#N>CO>[C:22]([C:21]1[CH:24]=[CH:25][C:18]([CH2:16][N:5]2[CH2:6][CH:7]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:8]2)=[CH:19][CH:20]=1)#[N:23]

参加物

6

反応物 4

HCID 5975CyanideHCID 660424-CyanobenzaldehydeHCID 5003444Sodium cyanoborohydrideHCID 66677484tert-Butyl azetidine-3-carboxylate acetate

生成物 1

HCID 58504367tert-Butyl 1-(4-cyanobenzyl)azetidine-3-carboxylate収率 89%

試薬・触媒・溶媒 1

HCID 887Methanol溶媒

反応条件

温度
0 °C

実験手順

To a solution of tert-butyl azetidine-3-carboxylate acetic acid salt (92.0 g, 0.423 mol) in methanol (1.0 L) at room temperature was added 4-formylbenzonitrile (50.8 g, 0.381 mol). The reaction mixture was cooled to 0° C., and sodium cyanoborohydride (28.8 g, 0.458 mol) was added portion-wise (caution: potential cyanide generation). The reaction mixture was allowed to warm to room temperature and was stirred overnight. The reaction mixture was concentrated under reduced pressure, and the residue was diluted with a 10% aqueous solution of sodium bicarbonate and extracted with ethyl acetate. The organic layer was collected, washed with brine, and dried over anhydrous sodium sulfate. Concentration under reduced pressure followed by purification by silica gel chromatography using a 20% mixture of ethyl acetate in petroleum ether afforded tert-butyl 1-(4-cyanobenzyl)azetidine-3-carboxylate (89%) (After chromatography, Int. 1-D contained a small amount of 4-hydroxymethylbenzonitrile but was taken forward to the next step without further purification). LC/MS M+1=273.18. 1H NMR (400 MHz, CDCl3) δ ppm 1.46 (s, 9H), 3.22-3.31 (m, 3H), 3.48-3.56 (m, 2H), 3.66 (s, 2H), 7.39 (d, J=8.28 Hz, 2H), and 7.60 (d, J=8.28 Hz, 2H).

後処理

  1. temperatureto warm to room temperature
  2. concentrationThe reaction mixture was concentrated under reduced pressure
  3. additionthe residue was diluted with a 10% aqueous solution of sodium bicarbonate
  4. extractionextracted with ethyl acetate
  5. customThe organic layer was collected
  6. washwashed with brine
  7. dry with materialdried over anhydrous sodium sulfate
  8. concentrationConcentration under reduced pressure
  9. customfollowed by purification by silica gel chromatography

出典と根拠

ORDレコード
ord-9064b63eea4e4b8994c2e092958818a7
出典データセット
uspto-grants-2013_03
特許番号
US08404672B2

反応ノート

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