Dimethylformamide → (R)-3-(Methoxymethylcarbamoyl)pyrrolidine-1-carboxylic Acid t-Butyl Ester

HRID 885620ノート

反応式

HRID 885620 の反応式
[CH3:1][C:2]([O:5][C:6]([N:8]1[CH2:12][C@H:11]([C:13]([OH:15])=O)[CH2:10][CH2:9]1)=[O:7])([CH3:4])[CH3:3].C[N:17]([C:19]([O:23]N1N=NC2C=CC(=CC1=2)Cl)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH:41]1C=CC2N(O)N=NC=2C=1.Cl.CNOC.CN(C=O)C.CCN(C(C)C)C(C)C>C([O-])(O)=O.[Na+]>[C:2]([O:5][C:6]([N:8]1[CH2:9][CH2:10][C@@H:11]([C:13](=[O:15])[NH:17][CH2:19][O:23][CH3:41])[CH2:12]1)=[O:7])([CH3:1])([CH3:3])[CH3:4]

参加物

8

反応物 6

HCID 6228DimethylformamideHCID 757711-HydroxybenzotriazoleHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 81531DiisopropylethylamineHCID 1512491(3R)-1-[(tert-butoxy)carbonyl]pyrrolidine-3-carboxylic acidHCID 42624899O-(6-Chlorobenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate

生成物 1

HCID 66924734(R)-3-(Methoxymethylcarbamoyl)pyrrolidine-1-carboxylic Acid t-Butyl Ester収率 84.8%

試薬・触媒・溶媒 1

HCID 516892Sodium Bicarbonate溶媒

反応条件

温度
0 °C

実験手順

(R)-1-N-Boc-β-Proline (700 mg, 3.3 mmol; (R)-pyrrolidine-1,3-dicarboxylic acid 1-t-butyl ester), HCTU (1.7 g, 4.1 mmol), HOBt (622 mg, 4.1 mmol), N,O-dimethylhydroxylamine HCl (1.6 g, 16.3 mmol) and DMF (10.0 mL, 129 mmol) were combined and cooled at 0° C. using an ice bath. DIPEA (5.7 mL, 32.5 mmol) was added slowly over 5 minutes. The mixture was allowed to warm to room temperature and stirred for 15 hours. The mixture was then diluted with sat. NaHCO3 (75 mL) and extracted with EtOAc (2×100 mL). The combined organic layers were washed with sat. NaCl (50 mL) and water (50 mL), dried over Na2SO4, filtered, and concentrated under high vacuum to yield 1.6 g of the crude product, which was purified by flash chromatography (12 g column, 10-100% EtOAc in hexanes over 16 minutes), and placed under high vacuum for 15 minutes to yield 723 mg of the title compound.

後処理

  1. temperatureto warm to room temperature
  2. extractionextracted with EtOAc (2×100 mL)
  3. washThe combined organic layers were washed with sat. NaCl (50 mL) and water (50 mL)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under high vacuum
  7. customto yield 1.6 g of the crude product, which
  8. customwas purified by flash chromatography (12 g column, 10-100% EtOAc in hexanes over 16 minutes)
  9. waitplaced under high vacuum for 15 minutes

出典と根拠

ORDレコード
ord-3c122557102a49568b577b18aec984b4
出典データセット
uspto-grants-2012_08
特許番号
US08242164B2

反応ノート

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