Diethyl (cyanomethyl)phosphonate → HCID 71143653, 화합물

HRID 1049135노트

반응식

HRID 1049135 반응식
CC(C)([O-])C.[K+].[C:7]([CH2:9]P(=O)(OCC)OCC)#[N:8].[CH:18]([NH:21][C:22](=[O:34])[C:23]1[CH:28]=[CH:27][C:26]([N:29]2[CH2:32][C:31](=O)[CH2:30]2)=[CH:25][CH:24]=1)([CH3:20])[CH3:19]>O1CCCC1>[C:7]([CH:9]=[C:31]1[CH2:32][N:29]([C:26]2[CH:27]=[CH:28][C:23]([C:22]([NH:21][CH:18]([CH3:20])[CH3:19])=[O:34])=[CH:24][CH:25]=2)[CH2:30]1)#[N:8]

참가 물질

5

반응물 3

HCID 75676Diethyl (cyanomethyl)phosphonateHCID 23665647Potassium tert-butoxideHCID 71143526HCID 71143526, 화합물

생성물 1

HCID 71143653HCID 71143653, 화합물수율 42%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매3회

실험 절차

To a cooled (at −6-0° C.) solution of 1.0 M potassium tert-butoxide in tetrahydrofuran (7.10 mL, 7.10 mmol) was added dropwise a solution of diethyl cyanomethylphosphonate (1.20 mL, 7.43 mmol, from Aldrich) in tetrahydrofuran (10 mL) over a period of 10 min and at −6 to 0° C. The reaction was warmed and stirred at room temperature for 1 h. The reaction mixture was cooled at −6° C. again. To the reaction mixture was then added a solution of N-isopropyl-4-(3-oxoazetidin-1-yl)benzamide (1.30 g, 5.60 mmol) in tetrahydrofuran (10 mL) over a period of 10 min. During this time the temperature of the reaction mixture was between −5 to 0° C. The reaction was allowed to warm to room temperature and was stirred for 3 h. The reaction mixture was filtered through a pad of silica gel and washed with ethyl acetate. The filtrate was concentrated, and the residue was treated with ether. The precipitates formed were collected by filtration to give 0.60 g the desired product. The mother liquid was concentrated under reduced pressure. The residue was purified by flash chromatography on a silica gel column eluting with ethyl acetate in hexane (gradient: 30-80%) to afford the desired product (0.21 g). The total product is 0.81 g (57%). 1H NMR (400 MHz, DMSO-d6) δ 7.91 (d, J=7.8 Hz, 1H), 7.74 (d, J=8.7 Hz, 2H), 6.53 (d, J=8.7 Hz, 2H), 5.88 (p, J=2.3 Hz, 1H), 4.77-4.67 (m, 2H), 4.62 (dt, J=5.1, 2.6 Hz, 2H), 4.06 (m, 1H), 1.12 (d, J=6.6 Hz, 6H) ppm. LCMS cacld. for C15H18N3O (M+1)+: m/z=256.1. Found: 256.1.

후처리

  1. customat −6 to 0° C
  2. temperatureThe reaction was warmed
  3. temperatureThe reaction mixture was cooled at −6° C. again
  4. customwas between −5 to 0° C
  5. temperatureto warm to room temperature
  6. stirringwas stirred for 3 h
  7. filtrationThe reaction mixture was filtered through a pad of silica gel
  8. washwashed with ethyl acetate
  9. concentrationThe filtrate was concentrated
  10. additionthe residue was treated with ether
  11. customThe precipitates formed
  12. filtrationwere collected by filtration

출처 및 근거

ORD 기록
ord-5359a9b3f9cb44f3a37971d8215c4d0b
출처 데이터셋
uspto-grants-2016_07
특허 번호
US09382231B2

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