Benzoic Acid → HCID 86665290, compound

HRID 1970850Notes

Reaction equation

HRID 1970850 reaction equation
[NH2:1][C:2]1[C:7]([Cl:8])=[CH:6][C:5]([C:9]([OH:18])([C:14]([F:17])([F:16])[F:15])[C:10]([F:13])([F:12])[F:11])=[CH:4][C:3]=1[Br:19].[C:20](O)(=[O:27])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.N1C=CC=CC=1.O=C1N([ClH]P([ClH]N2CCOC2=O)=O)CCO1>ClCCl>[NH2:1][C:2]1[C:7]([Cl:8])=[CH:6][C:5]([C:9]([O:18][C:20](=[O:27])[C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)([C:10]([F:11])([F:12])[F:13])[C:14]([F:17])([F:15])[F:16])=[CH:4][C:3]=1[Br:19]

Participants

5

Reactant 3

HCID 243Benzoic AcidHCID 1049PyridineHCID 86665291HCID 86665291, compound

Product 1

HCID 86665290HCID 86665290, compoundYield 42%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 2-(4-amino-3-bromo-5-chlorophenyl)-1,1,1,3,3,3-hexafluoropropan-2-ol (Example 3.3) (3.725 g, 10.0 mmol) and benzoic acid (1.28 g, 10.5 mmol) in dichloromethane (30 ml) was added pyridine (4.18 ml, 30 mmol) and bis(2-oxo-3-oxazolidinyl)phosphonic chloride (“BOP-Cl”) (2.80 g, 11 mmol). The reaction mixture was heated to reflux for 24 hours. The reaction mixture was cooled to ambient temperature and quenched by addition of aqueous hydrochloric acid (1N) (50 ml). The mixture was then extracted three times with dichloromethane. The combined organic extracts were washed with saturated aqueous sodium hydrogen carbonate, dried over sodium sulfate and concentrated. The residue was purified by column chromatography on silica gel (Buchi fraction collector C-660, prepacked cartridges Silicagel 60, particle size: 40-63 μm, D 40×150 mm, Gradient 99 to 1% methanol in toluene over 15 min, 60 mL/min, fraction 20 mL) to give benzoic acid 1-(4-amino-3-bromo-5-chlorophenyl)-2,2,2-trifluoro-1-trifluoromethylethyl ester (2 g, 42% yield). 1H NMR (400 MHz, CDCl3): 8.18 (d, 1H), 8.11 (d, 1H), 7.68 (m, 1H), 7.53 (m, 2H), 7.41 (s, 1H), 7.29 (s, 1H), 4.74 (bs, 2H).

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureto reflux for 24 hours
  3. customquenched by addition of aqueous hydrochloric acid (1N) (50 ml)
  4. extractionThe mixture was then extracted three times with dichloromethane
  5. washThe combined organic extracts were washed with saturated aqueous sodium hydrogen carbonate
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated
  8. customThe residue was purified by column chromatography on silica gel (Buchi fraction collector C-660, prepacked cartridges Silicagel 60, particle size: 40-63 μm, D 40×150 mm, Gradient 99 to 1% methanol in toluene over 15 min, 60 mL/min, fraction 20 mL)

Sources & evidence

ORD record
ord-914fb559b8f34cf283a8095e40b92e75
Source dataset
uspto-grants-2013_04
Patent number
US08431514B2

Reaction notes

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