Ammonia → HCID 86719487, compound

HRID 1772253Notes

Reaction equation

HRID 1772253 reaction equation
[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([NH:10][CH:11]2[CH2:16][CH2:15][CH:14]([O:17][CH2:18][C:19](O)=[O:20])[CH2:13][CH2:12]2)=[CH:6][C:5]=1[C:22]([F:25])([F:24])[F:23])([O-:3])=[O:2].C1N=C[N:28](C(N2C=NC=C2)=O)C=1.N>O1CCCC1.O>[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([NH:10][CH:11]2[CH2:12][CH2:13][CH:14]([O:17][CH2:18][C:19]([NH2:28])=[O:20])[CH2:15][CH2:16]2)=[CH:6][C:5]=1[C:22]([F:23])([F:24])[F:25])([O-:3])=[O:2]

Participants

6

Reactant 3

HCID 222AmmoniaHCID 682631,1'-CarbonyldiimidazoleHCID 672837722-(4-(4-Nitro-3-(trifluoromethyl)phenylamino)cyclohexyloxy)acetic acid

Product 1

HCID 86719487HCID 86719487, compoundYield 74%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

To a heated solution (60° C.) of 2-[(4-[[4-nitro-3-(trifluoromethyl)phenyl]amino]cyclohexyl)oxy]acetic acid (300 mg, 0.83 mmol) in tetrahydrofuran (25 ml) was added CDI (300 mg, 1.85 mmol, 2.2 eq) at reflux and then stirred for 1 hour at 60° C. (oil bath temperature). The resulting solution was poured into ammonia (25 ml) at room temperature and stirred for an additional 1 hour. The contents were diluted with water (100 ml) and the resulting mixture was extracted with ethyl acetate (3×100 ml). The organic layers were combined, washed with saturated aqueous sodium chloride (100 ml), dried over anhydrous sodium sulfate, filtered, and then concentrated under vacuum to afford 2-[(4-[[4-nitro-3-(trifluoromethyl)phenyl]amino]cyclohexyl)oxy]acetamide as yellow solid (220 mg, 74%). (ES, m/z) [M+H]+ 362; 1H NMR (300 MHz, DMSO): δ 8.06 (d, J=9.0 Hz, 1H), 7.48 (d, J=7.8 Hz, 1H), 7.27 (d, J=4.2 Hz, 1H), 7.07 (s, 2H), 6.85 (dd, J=2.4 Hz, 9.3 Hz, 1H), 3.82 (s, 2H), 3.40-3.55 (m, 2H), 1.90-2.10 (m, 4H), 1.10-1.50 (m, 4H)

Workup

  1. temperatureat reflux
  2. stirringstirred for an additional 1 hour
  3. extractionthe resulting mixture was extracted with ethyl acetate (3×100 ml)
  4. washwashed with saturated aqueous sodium chloride (100 ml)
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-492e71ee86214f4e94a6b50dab25576b
Source dataset
uspto-grants-2016_02
Patent number
US09249102B2

Reaction notes

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