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

HRID 1364996노트

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HRID 1364996 반응식
[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]

참가 물질

8

반응물 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

생성물 1

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

시약·촉매·용매 1

HCID 516892Sodium Bicarbonate용매

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온도
0 °C

실험 절차

(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-dimethyl-hydroxylamine 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.

후처리

  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

출처 및 근거

ORD 기록
ord-321eb0482a2b488e967abb3fb60897f8
출처 데이터셋
uspto-grants-2011_02
특허 번호
US07888386B2

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