Toluene → HCID 90036487, compound

HRID 1055386Notes

Reaction equation

HRID 1055386 reaction equation
[CH2:1]([N:8]([CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[CH:9]([C:13]1([OH:19])[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]1)[C:10]([OH:12])=[O:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.F[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=1[N+:34]([O-])=O.C[Si]([N-][Si](C)(C)C)(C)C.[K+].C1(C)C=CC=CC=1.OS([O-])(=O)=O.[K+]>C1COCC1.O>[NH2:34][C:29]1[CH:30]=[CH:31][CH:32]=[CH:33][C:28]=1[O:19][C:13]1([CH:9]([N:8]([CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)[CH2:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[C:10]([OH:12])=[O:11])[CH2:14][CH2:15][CH2:16][CH2:17][CH2:18]1

Participants

8

Reactant 5

HCID 1140TolueneHCID 738951-Fluoro-2-nitrobenzene2×HCID 516920Potassium bisulfateHCID 3251421Potassium bis(trimethylsilyl)amide2×HCID 90037501HCID 90037501, compound

Product 1

HCID 90036487HCID 90036487, compoundYield 90.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

2-(dibenzylamino)-2-(1-hydroxycyclohexyl)acetic acid (0.70 g, 1.98 mmol, Eq: 1.00) and 1-fluoro-2-nitrobenzene (293 mg, 219 μl, 2.08 mmol, Eq: 1.05) were dissolved in THF (10 mL) and a solution of potassium bis(trimethylsilyl)amide 0.5 M in toluene (8.71 mL, 4.36 mmol, Eq: 2.2) was added. The mixture was heated to 60° C. After 1 h the mixture was cooled to RT and 0.2 mL 1-fluoro-2-nitrobenzene and an additional 9 mL of potassium bis(trimethylsilyl)amide (0.5 M in toluene) were added and the mixture stirred at 60° C. for 90 min. The mixture was diluted with H2O, acidified with sat. KHSO4, and extracted with EtOAc. The combined extracts were washed with H2O, brine, dried over Na2SO4 and concentrated. The residue was purified by flash chromatography to afford 2-(1-(2-aminophenoxyl)cyclohexyl)-2-(dibenzylamino)acetic acid as a light brown oil (0.80 g, 85%). MS m/z 475.1 (MH+)

Workup

  1. temperatureAfter 1 h the mixture was cooled to RT
  2. extractionextracted with EtOAc
  3. washThe combined extracts were washed with H2O, brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated
  6. customThe residue was purified by flash chromatography

Sources & evidence

ORD record
ord-bdaa980d9f1e4d1cb7a8e76f070d3121
Source dataset
uspto-grants-2016_07
Patent number
US09394263B2

Reaction notes

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