4-Methylmorpholine → HCID 57914338, compound

HRID 2283580Notes

Reaction equation

HRID 2283580 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1[CH:14]=[CH:13][C:12]([C:15]([OH:17])=O)=[C:11]([OH:18])[CH:10]=1.C1(N=C=NC2CCCCC2)CCCCC1.CN1CCOCC1.[N:41]([CH2:44][CH2:45][NH2:46])=[N+:42]=[N-:43]>O.CN(C)C=O>[N:41]([CH2:44][CH2:45][NH:46][C:15]([C:12]1[CH:13]=[CH:14][C:9]([C:3]2[CH:4]=[CH:5][C:6]([F:8])=[CH:7][C:2]=2[F:1])=[CH:10][C:11]=1[OH:18])=[O:17])=[N+:42]=[N-:43]

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 10868DicyclohexylcarbodiimideHCID 55649Ethylamine, 2-azido-HCID 120503722',4'-difluoro-3-hydroxybiphenyl-4-carboxylic acid

Product 1

HCID 57914338HCID 57914338, compoundYield 61%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To a 25 mL round-bottomed flask equipped with a magnetic stir bar was added 2′,4′-difluoro-3-hydroxybiphenyl-4-carboxylic acid (0.301, 1.20 mmol), N,N-Dimethylformamide (5 mL), N,N′-Dicyclohexylcarbodiimide (0.248 g, 1.20 mmol) and n-methylmorpholine (0.25 mL). The reaction mixture was cooled to 0° C. and allowed to stir. Then, 2-azidoethanamine (0.1037 g, 1.20 mmol) was added dropwise and allowed to slowly warm to room temperature while stirring for 24 hr. The reaction mixture was diluted with water, extracted with dichloromethane, washed with 1N HCl, washed with saturated sodium bicarbonate, washed with brine and then concentrated de vacuo. The resulting residue was then purified via silica gel column chromatography (1:40 methanol:dichloromethane to 1:10 methanol:dichloromethane) to give N-(2-azidoethyl)-2′,4′-difluoro-3-hydroxybiphenyl-4-carboxamide (0.232 g, 61% yield). 1H NMR (300 MHz, CDCl3) δ 7.60 (s, 1H), δ 7.47 (d, 1H), δ 7.29 (m, 2H), δ 7.02 (d, 1H), δ 6.88 (m, 2H) ppm; 13C NMR (75 MHz, CDCl3) δ 170.3, 160.8, 135.1, 131.3, 131.2, 131.3, 131.2, 126.8, 118.8, 114.6, 112.0, 111.8, 104.8, 104.6, 104.3, 50.7, 39.3 ppm; HRMS (ESI) calcd for C15H12F2N4O3(M+) 318.0928. Found 318.0933.

Workup

  1. customTo a 25 mL round-bottomed flask equipped with a magnetic stir bar
  2. temperatureto slowly warm to room temperature
  3. stirringwhile stirring for 24 hr
  4. extractionextracted with dichloromethane
  5. washwashed with 1N HCl
  6. washwashed with saturated sodium bicarbonate
  7. washwashed with brine
  8. concentrationconcentrated de vacuo
  9. customThe resulting residue was then purified via silica gel column chromatography (1:40 methanol:dichloromethane to 1:10 methanol:dichloromethane)

Sources & evidence

ORD record
ord-5df08a50d5044e2889cd637624c94729
Source dataset
uspto-grants-2015_09
Patent number
US09145395B2

Reaction notes

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