Hydrochloric Acid → 3-[4-(Azetidin-1-ylcarbonyl)-2-fluorophenoxy]-5-[(1S)-2-hydroxy-1-methylethoxy]-N-(3-methyl-1,2,4-thiadiazol-5-yl)benzamide

HRID 20581Notes

Reaction equation

HRID 20581 reaction equation
Cl.[N:2]1([C:6]([C:8]2[CH:41]=[CH:40][C:11]([O:12][C:13]3[CH:14]=[C:15]([CH:25]=[C:26]([O:28][C@@H:29]([CH3:39])[CH2:30][O:31][Si](C(C)(C)C)(C)C)[CH:27]=3)[C:16]([NH:18][C:19]3[S:23][N:22]=[C:21]([CH3:24])[N:20]=3)=[O:17])=[C:10]([F:42])[CH:9]=2)=[O:7])[CH2:5][CH2:4][CH2:3]1.C(=O)(O)[O-].[Na+]>CO>[N:2]1([C:6]([C:8]2[CH:41]=[CH:40][C:11]([O:12][C:13]3[CH:14]=[C:15]([CH:25]=[C:26]([O:28][C@@H:29]([CH3:39])[CH2:30][OH:31])[CH:27]=3)[C:16]([NH:18][C:19]3[S:23][N:22]=[C:21]([CH3:24])[N:20]=3)=[O:17])=[C:10]([F:42])[CH:9]=2)=[O:7])[CH2:3][CH2:4][CH2:5]1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 516892Sodium BicarbonateHCID 593468823-[4-(azetidin-1-ylcarbonyl)-2-fluorophenoxy]-5-((1S)-2-{[tert-butyl(dimethyl)silyl]oxy}-1-methylethoxy)-N-(3-methyl-1,2,4-thiadiazol-5-yl)benzamide

Product 1

HCID 117200553-[4-(Azetidin-1-ylcarbonyl)-2-fluorophenoxy]-5-[(1S)-2-hydroxy-1-methylethoxy]-N-(3-methyl-1,2,4-thiadiazol-5-yl)benzamideYield 52%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

10% Hydrochloric acid (2 mL) was added to a solution of 3-[4-(azetidin-1-ylcarbonyl)-2-fluorophenoxy]-5-((1S)-2-{[tert-butyl(dimethyl)silyl]oxy}-1-methylethoxy)-N-(3-methyl-1,2,4-thiadiazol-5-yl)benzamide (950 mg, 1.58 mmol) in methanol (20 mL). The reaction was stirred at ambient temperature for 1 hour, saturated sodium bicarbonate solution added and the methanol evaporated. The aqueous residue was taken to pH2 and extracted with ethyl acetate. The extracts were combined, washed with brine, dried (MgSO4), filtered and evaporated in vacuo to give the crude product which was chromatographed on silica, eluting with ethyl acetate, to give the desired compound (400 mg) which was recrystallised from ethyl acetate (mpt 173° C.-175° C.).

Workup

  1. customthe methanol evaporated
  2. extractionextracted with ethyl acetate
  3. washwashed with brine
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. customevaporated in vacuo
  7. customto give the crude product which
  8. customwas chromatographed on silica
  9. washeluting with ethyl acetate

Sources & evidence

ORD record
ord-a0fd83da55a34518ba3c211f4b2d24ab
Source dataset
uspto-grants-2010_06
Patent number
US07745475B2

Reaction notes

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