Hydrochloric Acid → N-((1R)-1-{4-[(hydroxyamino)carbonyl]phenyl}ethyl)-1-benzofuran-2-carboxamide

HRID 1049080Notes

Reaction equation

HRID 1049080 reaction equation
[O:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[CH:3]=[C:2]1[C:10]([NH:12][C@@H:13]([C:15]1[CH:27]=[CH:26][C:18]([C:19](OC(C)(C)C)=[O:20])=[CH:17][CH:16]=1)[CH3:14])=[O:11].FC(F)(F)C(O)=O.CN(C([O:42][N:43]1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)CC)C.[Si](ON)(C(C)(C)C)(C)C.Cl>CS(C)=O.C(Cl)Cl>[OH:42][NH:43][C:19]([C:18]1[CH:26]=[CH:27][C:15]([C@H:13]([NH:12][C:10]([C:2]2[O:1][C:5]3[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=3[CH:3]=2)=[O:11])[CH3:14])=[CH:16][CH:17]=1)=[O:20]

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 4691350O-(tert-Butyldimethylsilyl)hydroxylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 67395671tert-butyl 4-{(1R)-1-[(1-benzofuran-2-ylcarbonyl)amino]ethyl}benzoate

Product 1

HCID 86657276N-((1R)-1-{4-[(hydroxyamino)carbonyl]phenyl}ethyl)-1-benzofuran-2-carboxamideYield 24%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a 2-dram vial containing tert-butyl 4-{(1R)-1-[(1-benzofuran-2-ylcarbonyl)amino]ethyl}benzoate was added DCM (2.5 mL), and trifluoroacetic acid (0.28 mL, 3.60 mmol). The mixture was stirred at rt for 6 h then evaporated to give an oil residue. To the residue was added HATU (0.10 g, 0.27 mmol), triethylamine (0.25 mL, 1.80 mmol), and DCM (2.5 mL). After stirring at rt for 30 min, O-(tert-butyldimethylsilyl)hydroxylamine (0.053 g, 0.360 mmol) was added. The mixture was stirred at rt for 2 h, then the solvent was completely removed to give a sticky brown oil. To this oil residue was added hydrochloric acid (4.0 mL, 1% v/v in IPA). After stirring at rt for 30 min, the solvent was evaporated to dryness to give a solid. To the solid was then added DMSO (1.1 mL). The solution was filtered and purified by Gilson prep-HPLC [25-50% MeCN—H2O] to give N-((1R)-1-{4-[(hydroxyamino)carbonyl]phenyl}ethyl)-1-benzofuran-2-carboxamide (0.0148 g, 24%) as a white solid. LC-MS: (FA) ES+ 325; 1H NMR (Methanol-d4, 400 MHz) δ 7.71 (m, 3H), 7.60 (d, J=8.5 Hz, 1H), 7.50 (m, 3H), 7.45 (t, J=7.0 Hz, 1H), 7.31 (t, J=7.8 Hz, 1H), 5.30 (q, J=7.2 Hz, 1H), 1.61 (d, J=7.0 Hz, 3H).

Workup

  1. customthen evaporated
  2. customto give an oil residue
  3. stirringAfter stirring at rt for 30 min
  4. stirringThe mixture was stirred at rt for 2 h
  5. customthe solvent was completely removed
  6. customto give a sticky brown oil
  7. stirringAfter stirring at rt for 30 min
  8. customthe solvent was evaporated to dryness
  9. customto give a solid
  10. filtrationThe solution was filtered
  11. custompurified by Gilson prep-HPLC [25-50% MeCN—H2O]

Sources & evidence

ORD record
ord-d02457ca831041adae5837fe8d23069a
Source dataset
uspto-grants-2016_07
Patent number
US09382197B2

Reaction notes

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