5-Aminosalicylic Acid → HCID 71243638, compound

HRID 1774466Notes

Reaction equation

HRID 1774466 reaction equation
[OH:1][C@H:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][C@:3]1([CH2:20][C:21]1[CH:31]=[CH:30][C:24]([C:25](OCC)=[O:26])=[CH:23][CH:22]=1)[C:11]1[CH2:12][C:13]2[C:18]([CH:19]=1)=[CH:17][CH:16]=[CH:15][CH:14]=2.[NH2:32][C:33]1[CH:34]=[CH:35][C:36]([OH:42])=[C:37]([CH:41]=1)[C:38]([OH:40])=[O:39].C[Al](C)C>C1COCC1>[OH:42][C:36]1[CH:35]=[CH:34][C:33]([NH:32][C:25](=[O:26])[C:24]2[CH:23]=[CH:22][C:21]([CH2:20][C@:3]3([C:11]4[CH2:12][C:13]5[C:18]([CH:19]=4)=[CH:17][CH:16]=[CH:15][CH:14]=5)[CH2:4][C:5]4[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=4)[C@@H:2]3[OH:1])=[CH:31][CH:30]=2)=[CH:41][C:37]=1[C:38]([OH:40])=[O:39]

Participants

5

Reactant 3

HCID 40755-Aminosalicylic AcidHCID 16682925TrimethylaluminumHCID 71243533HCID 71243533, compound

Product 1

HCID 71243638HCID 71243638, compoundYield 30.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a mixture of ethyl 4-(((1R,2R)-1-hydroxy-2,3-dihydro-1H,1′H-[2,2′-biinden]-2-yl)methyl)benzoate (11, 200 mg, 0.48 mmol), 5-amino-2-hydroxybenzoic acid (75 mg, 0.48 mmol) and THF (1.0 mL) in a 5 mL microwave vial, was added trimethylaluminium (0.5 mL, 20% solution in toluene) and the mixture irradiated at 100° C. for 5 min. The reaction mixture was quenched with slow addition of 1.5 N HCl (2 mL) and extracted with ethyl acetate (3×15 mL). Organic layer was washed with water (25 mL), brine (25 mL), dried over anhydrous Na2SO4 and evaporated under reduced pressure. The residue purified by preparative HPLC [Kromasil C18 (250×50 mm), flow rate: 40 mL/min, 0.1% TFA in water/MeOH, run time: 40 min] to yield 75 mg (30%) of the title compound as an off white solid.

Workup

  1. customthe mixture irradiated at 100° C. for 5 min
  2. customThe reaction mixture was quenched with slow addition of 1.5 N HCl (2 mL)
  3. extractionextracted with ethyl acetate (3×15 mL)
  4. washOrganic layer was washed with water (25 mL), brine (25 mL)
  5. dry with materialdried over anhydrous Na2SO4
  6. customevaporated under reduced pressure
  7. customThe residue purified by preparative HPLC [Kromasil C18 (250×50 mm), flow rate: 40 mL/min, 0.1% TFA in water/MeOH, run time: 40 min]

Sources & evidence

ORD record
ord-1d75acdd0bcf4b519373afea5472b97d
Source dataset
uspto-grants-2016_02
Patent number
US09260376B2

Reaction notes

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