Glycolic Acid → HCID 23729264, compound

HRID 1676147Notes

Reaction equation

HRID 1676147 reaction equation
[CH2:1]([C:5]1[CH:6]=[C:7]([C:11]2[O:15][N:14]=[C:13]([C:16]3[CH:27]=[CH:26][C:19]([O:20][CH2:21][CH:22]([OH:25])[CH2:23]O)=[CH:18][C:17]=3[O:28][CH3:29])[N:12]=2)[S:8][C:9]=1[CH3:10])[CH:2]([CH3:4])[CH3:3].CC[N:32](C(C)C)C(C)C.CS(Cl)(=O)=O.[C:44]([OH:48])(=O)[CH2:45][OH:46].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F>C1COCC1>[OH:46][CH2:45][C:44]([NH:32][CH2:23][CH:22]([OH:25])[CH2:21][O:20][C:19]1[CH:26]=[CH:27][C:16]([C:13]2[N:12]=[C:11]([C:7]3[S:8][C:9]([CH3:10])=[C:5]([CH2:1][CH:2]([CH3:3])[CH3:4])[CH:6]=3)[O:15][N:14]=2)=[C:17]([O:28][CH3:29])[CH:18]=1)=[O:48]

Participants

7

Reactant 5

HCID 757Glycolic AcidHCID 31297Methanesulfonyl chloride2×HCID 81531Diisopropylethylamine3×HCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 23729263HCID 23729263, compound

Product 1

HCID 23729264HCID 23729264, compoundYield 29.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a solution of rac-3-{4-[5-(4-isobutyl-5-methyl-thiophen-2-yl)-[1,2,4]oxadiazol-3-yl]-3-methoxy-phenoxy}-propane-1,2-diol (400 mg, 0.956 mmol) and DIPEA (257 mg, 1.99 mmol) in THF (40 mL), methanesulfonylchloride (125 mg, 1.095 mmol) dissolved in THF (10 mL) is added at −10° C. The reaction is allowed to warm to rt and is stirred for 15 h. Another portion of methanesulfonylchloride (30 mg, 0.258 mmol) in THF (2 mL) and DIPEA (128 mg, 0.993 mmol) is added and stirring is continued for 24 h. The mixture is evaporated and the residue is dissolved in 7 N NH3 in MeOH (17 mL). The resulting solution is stirred at 70° C. for 5 h before it is evaporated. The remaining residue is dissolved in DMF (15 mL) and glycolic acid (110 mg, 1.45 mmol), DIPEA (257 mg, 1.99 mmol) and TBTU (370 mg, 1.15 mmol) is added. The mixture is stirred at rt for 5 h, evaporated and the residue is purified on prep. TLC plates with EA to give 2-hydroxy-N-(2-hydroxy-3-{4-[5-(4-isobutyl-5-methyl-thiophen-2-yl)-[1,2,4]oxadiazol-3-yl]-3-methoxy-phenoxy}-propyl)-acetamide (135 mg) as colourless foam; LC-MS: tR=0.95 min, [M+1]=476.29; 1H NMR (D6-acetone): δ 7.92 (d, J=8.8 Hz, 1H), 7.71 (s, 1H), 7.57 (s br, 1H), 6.77 (d, J=2.3 Hz, 1H), 6.71 (dd, J=2.3, 8.8 Hz, 1H), 4.74-4.67 (m, 2H), 4.15-4.07 (m, 3H), 3.99 (d, J=5.0 Hz, 2H), 3.93 (s, 3H), 3.66-3.57 (m, 1H), 3.48-3.39 (m, 1H), 2.52 (d, J=7.0 Hz, 2H), 2.49 (s, 3H), 1.95 (hept, J=7.0 Hz, 1H), 0.95 (d, J=6.4 Hz, 6H).

Workup

  1. additionis added at −10° C
  2. stirringstirring
  3. waitis continued for 24 h
  4. customThe mixture is evaporated
  5. dissolutionthe residue is dissolved in 7 N NH3 in MeOH (17 mL)
  6. stirringThe resulting solution is stirred at 70° C. for 5 h before it
  7. customis evaporated
  8. dissolutionThe remaining residue is dissolved in DMF (15 mL)
  9. stirringThe mixture is stirred at rt for 5 h
  10. customevaporated
  11. customthe residue is purified on prep

Sources & evidence

ORD record
ord-ba7aedbba51147ae951b5f267f492244
Source dataset
uspto-grants-2011_08
Patent number
US08003800B2

Reaction notes

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