Cesium carbonate → methyl 2-[[3,5-bis(trifluoromethyl)benzoyl]amino]-4-[3-[(E)-(4-tert-butylphenyl)methylideneamino]oxypropoxy]benzoate

HRID 29671Notes

Reaction equation

HRID 29671 reaction equation
[CH3:1][O:2][C:3](=[O:32])[C:4]1[CH:9]=[CH:8][C:7]([O:10][CH2:11][CH2:12][CH2:13]Br)=[CH:6][C:5]=1[NH:15][C:16](=[O:31])[C:17]1[CH:22]=[C:21]([C:23]([F:26])([F:25])[F:24])[CH:20]=[C:19]([C:27]([F:30])([F:29])[F:28])[CH:18]=1.[C:33]([C:37]1[CH:45]=[CH:44][C:40]([CH:41]=[N:42][OH:43])=[CH:39][CH:38]=1)([CH3:36])([CH3:35])[CH3:34].C(=O)([O-])[O-].[Cs+].[Cs+]>CC(C)=O>[CH3:1][O:2][C:3](=[O:32])[C:4]1[CH:9]=[CH:8][C:7]([O:10][CH2:11][CH2:12][CH2:13][O:43]/[N:42]=[CH:41]/[C:40]2[CH:44]=[CH:45][C:37]([C:33]([CH3:36])([CH3:35])[CH3:34])=[CH:38][CH:39]=2)=[CH:6][C:5]=1[NH:15][C:16](=[O:31])[C:17]1[CH:22]=[C:21]([C:23]([F:26])([F:25])[F:24])[CH:20]=[C:19]([C:27]([F:30])([F:29])[F:28])[CH:18]=1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 1275951N-[(4-tert-butylphenyl)methylidene]hydroxylamineHCID 865974012-(3,5-Bis-trifluoromethyl-benzoylamino)-4-(3-bromo-propoxy)-benzoic acid methyl ester

Product 1

HCID 87733702methyl 2-[[3,5-bis(trifluoromethyl)benzoyl]amino]-4-[3-[(E)-(4-tert-butylphenyl)methylideneamino]oxypropoxy]benzoateYield 48%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

To a solution of 2-(3,5-bis-trifluoromethyl-benzoylamino)-4-(3-bromo-propoxy)-benzoic acid methyl ester (0.53 g, 1.00 mmol) and 4-tert-butyl-benzaldehyde oxime (0.20 g, 1.10 mmol) in acetone (35 mL) was added cesium carbonate (1.30 g, 4.00 mmol). The mixture was heated to reflux overnight and then allowed to cool back to room temperature. The mixture was partitioned between ethyl acetate and brine and the layers were then separated. The aqueous layer was extracted with two additional portions of ethyl acetate. The organics were combined, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The crude oil was purified by flash chromatography through silica gel using diethyl ether/hexanes (0/100 gradient to 5/95) to give 2-{[3,5-bis(trifluoromethyl)benzoyl]amino}-4-[3-({[(1E)-(4-tert-butylphenyl)methylidene]amino}oxy)propoxy]benzoic acid methyl ester (0.30 g, 48%) as an off-white solid. 1H NMR (400 MHz, CDCl3); δ 12.52 (s, 1H), 8.51 (d, 1H), 8.48 (s, 2H), 8.06 (s, 1H), 8.04 (s, 1H), 7.99 (d, 1H), 7.47-7.35 (AA′BB′, 4H), 6.67 (dd, 1H), 4.34 (t, 2H), 4.22 (t, 2H), 3.92 (s, 3H), 2.23 (m, 2H), 1.28 (s, 9H).

Workup

  1. temperatureThe mixture was heated
  2. temperatureto reflux overnight
  3. customThe mixture was partitioned between ethyl acetate and brine
  4. customthe layers were then separated
  5. extractionThe aqueous layer was extracted with two additional portions of ethyl acetate
  6. dry with materialdried over anhydrous magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe crude oil was purified by flash chromatography through silica gel

Sources & evidence

ORD record
ord-69efc2c2b6f245f698f79ec785244b9d
Source dataset
uspto-grants-2008_09
Patent number
US07420083B2

Reaction notes

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