4-Methylmorpholine → HCID 57914338, compound

HRID 384207Notes

Reaction equation

HRID 384207 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 C1-15H12F2N4O3 (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-b6808e9da3674f40a94b61982fa9ee0b
Source dataset
uspto-grants-2013_02
Patent number
US08367713B2

Reaction notes

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