Diethyl (cyanomethyl)phosphonate → HCID 71143653, compound

HRID 1049135Notes

Reaction equation

HRID 1049135 reaction equation
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]

Participants

5

Reactant 3

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

Product 1

HCID 71143653HCID 71143653, compoundYield 42%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-5359a9b3f9cb44f3a37971d8215c4d0b
Source dataset
uspto-grants-2016_07
Patent number
US09382231B2

Reaction notes

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