Citric Acid → 3-[4-(azetidin-1-ylcarbonyl)-2-fluorophenoxy]-5-((1S)-2-{[tert-butyl(dimethyl)silyl]oxy}-1-methylethoxy)benzoic acid

HRID 20522Notes

Reaction equation

HRID 20522 reaction equation
[N:1]1([C:5]([C:7]2[CH:27]=[CH:26][C:10]([O:11][C:12]3[CH:13]=[C:14]([CH:18]=[C:19]([O:21][C@@H:22]([CH3:25])[CH2:23][OH:24])[CH:20]=3)[C:15]([OH:17])=[O:16])=[C:9]([F:28])[CH:8]=2)=[O:6])[CH2:4][CH2:3][CH2:2]1.[Si:29](Cl)([C:32]([CH3:35])([CH3:34])[CH3:33])([CH3:31])[CH3:30].N1C=CN=C1.C(=O)(O)[O-].[Na+].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>CN(C=O)C.C(OCC)C.O>[N:1]1([C:5]([C:7]2[CH:27]=[CH:26][C:10]([O:11][C:12]3[CH:13]=[C:14]([CH:18]=[C:19]([O:21][C@@H:22]([CH3:25])[CH2:23][O:24][Si:29]([C:32]([CH3:35])([CH3:34])[CH3:33])([CH3:31])[CH3:30])[CH:20]=3)[C:15]([OH:17])=[O:16])=[C:9]([F:28])[CH:8]=2)=[O:6])[CH2:4][CH2:3][CH2:2]1

Participants

9

Reactant 5

HCID 311Citric AcidHCID 795ImidazoleHCID 28928tert-Butyldimethylsilyl chlorideHCID 516892Sodium BicarbonateHCID 593468833-[4-(azetidin-1-ylcarbonyl)-2-fluorophenoxy]-5-[(1S)-2-hydroxy-1-methylethoxy]benzoic acid

Product 1

HCID 593469093-[4-(azetidin-1-ylcarbonyl)-2-fluorophenoxy]-5-((1S)-2-{[tert-butyl(dimethyl)silyl]oxy}-1-methylethoxy)benzoic acid

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent

Procedure

A mixture of 3-[4-(azetidin-1-ylcarbonyl)-2-fluorophenoxy]-5-[(1S)-2-hydroxy-1-methylethoxy]benzoic acid (9.8 g, 0.025 mol), t-butyldimethylsilylchloride (11.3 g, 0.075 mol) and imidazole (17.08 g, 0.25 mol) in DMF (100 mL) was stirred at RT for 24 hours. Water (100 mL) was added and the mixture extracted into diethyl ether (3×100 mL). The extracts were combined and washed with water (3×100 mL), brine (100 mL), dried (MgSO4), filtered, and evaporated in vacuo to give a golden oil. Saturated aqueous sodium bicarbonate (100 mL) and diethyl ether (100 mL) were added and stirred for 30 mins. The aqueous layer was acidified with 1M citric acid solution and extracted into diethyl ether (3×100 mL). The extracts were combined, dried (MgSO4), filtered, and evaporated in vacuo and the crude product chromatographed on silica, eluting with ethyl acetate, to give the desired compound. (6.32 g).

Workup

  1. extractionthe mixture extracted into diethyl ether (3×100 mL)
  2. washwashed with water (3×100 mL), brine (100 mL)
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. customevaporated in vacuo
  6. customto give a golden oil
  7. stirringstirred for 30 mins
  8. extractionextracted into diethyl ether (3×100 mL)
  9. dry with materialdried (MgSO4)
  10. filtrationfiltered
  11. customevaporated in vacuo
  12. customthe crude product chromatographed on silica
  13. washeluting with ethyl acetate

Sources & evidence

ORD record
ord-159f422bd884422f8a95d077a5d152fa
Source dataset
uspto-grants-2010_06
Patent number
US07745475B2

Reaction notes

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