Glycolic Acid → 2-{3-[2-(1-Glycoloylpiperidin-4-yl)-1,3-thiazol-4-yl]-4,5-dihydro-1,2-oxazol-5-yl}phenyl methanesulphonate

HRID 2206878Notes

Reaction equation

HRID 2206878 reaction equation
[Cl-].[CH3:2][S:3]([O:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1[CH:13]1[O:17][N:16]=[C:15]([C:18]2[N:19]=[C:20]([CH:23]3[CH2:28][CH2:27][NH2+:26][CH2:25][CH2:24]3)[S:21][CH:22]=2)[CH2:14]1)(=[O:5])=[O:4].[C:29](O)(=[O:32])[CH2:30][OH:31].C(N(C(C)C)CC)(C)C.F[B-](F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1>CN(C)C=O>[CH3:2][S:3]([O:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1[CH:13]1[O:17][N:16]=[C:15]([C:18]2[N:19]=[C:20]([CH:23]3[CH2:28][CH2:27][N:26]([C:30](=[O:31])[CH2:29][OH:32])[CH2:25][CH2:24]3)[S:21][CH:22]=2)[CH2:14]1)(=[O:4])=[O:5]

Participants

6

Reactant 4

HCID 757Glycolic AcidHCID 81531Diisopropylethylamine2×HCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 1178190674-[4-(5-{2-[(Methylsulphonyl)oxy]phenyl}-4,5-dihydro-1,2-oxazol-3-yl)-1,3-thiazol-2-yl]piperidinium chloride

Product 1

HCID 1178189592-{3-[2-(1-Glycoloylpiperidin-4-yl)-1,3-thiazol-4-yl]-4,5-dihydro-1,2-oxazol-5-yl}phenyl methanesulphonateYield 13%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To 4-[4-(5-{2-[(methylsulphonyl)oxy]phenyl}-4,5-dihydro-1,2-oxazol-3-yl)-1,3-thiazol-2-yl]piperidinium chloride (110 mg) in dimethylformamide (6 ml) were added, under argon, glycolic acid (19 mg), diisopropylethylamine (32 mg) and O-(benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium tetrafluoroborate (TBTU, 159 mg). Then diisopropylethylamine (64 mg) was added once again to the reaction mixture. The reaction mixture was stirred at room temperature for 1 h. Then ice-cold sodium hydrogencarbonate solution was added thereto, the mixture was filtered, and the aqueous phase was removed and extracted with dichloromethane. The combined organic phases were dried over magnesium sulphate and concentrated. Purification by column chromatography gave 2-{3-[2-(1-glycoloylpiperidin-4-yl)-1,3-thiazol-4-yl]-4,5-dihydro-1,2-oxazol-5-yl}phenyl methanesulphonate (15 mg, 12%).

Workup

  1. additionThen ice-cold sodium hydrogencarbonate solution was added
  2. filtrationthe mixture was filtered
  3. customthe aqueous phase was removed
  4. extractionextracted with dichloromethane
  5. dry with materialThe combined organic phases were dried over magnesium sulphate
  6. concentrationconcentrated
  7. customPurification by column chromatography

Sources & evidence

ORD record
ord-29f924e495514a5295bf132c3227b601
Source dataset
uspto-grants-2016_06
Patent number
US09375009B2

Reaction notes

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