Hydrochloric Acid → N-hydroxy-4-[(1R)-1-({[4-(trifluoromethyl)phenyl]sulfonyl}amino)ethyl]benzamide

HRID 1049083Notes

Reaction equation

HRID 1049083 reaction equation
[F:1][C:2]([F:29])([F:28])[C:3]1[CH:8]=[CH:7][C:6]([S:9]([NH:12][C@@H:13]([C:15]2[CH:27]=[CH:26][C:18]([C:19](OC(C)(C)C)=[O:20])=[CH:17][CH:16]=2)[CH3:14])(=[O:11])=[O:10])=[CH:5][CH:4]=1.FC(F)(F)C(O)=O.CN(C([O:44][N:45]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.C([O-])(O)=O.[Na+]>C(Cl)Cl.CN(C)C=O.C1(C)C=CC=CC=1.ClCCCl>[OH:44][NH:45][C:19](=[O:20])[C:18]1[CH:26]=[CH:27][C:15]([C@H:13]([NH:12][S:9]([C:6]2[CH:7]=[CH:8][C:3]([C:2]([F:29])([F:28])[F:1])=[CH:4][CH:5]=2)(=[O:11])=[O:10])[CH3:14])=[CH:16][CH:17]=1

Participants

12

Reactant 7

HCID 313Hydrochloric AcidHCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 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 67395467(R)-tert-butyl 4-(1-(4-(trifluoromethyl)phenylsulfonamido)ethyl)benzoate

Product 1

HCID 86657277N-hydroxy-4-[(1R)-1-({[4-(trifluoromethyl)phenyl]sulfonyl}amino)ethyl]benzamideYield 15%

Reagents, catalysts & solvents 4

HCID 111,2-DichloroethaneSolventHCID 1140TolueneSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a 2-dram vial containing (R)-tert-butyl 4-(1-(4-(trifluoromethyl)phenylsulfonamido)ethyl)benzoate was added 1,2-dichloroethane (2 mL), and trifluoroacetic acid (0.246 mL, 3.20 mmol). After shaking at rt for 4 h, the mixture was evaporated to dryness to give a residue which was azetroped with toluene (2×5 mL). To the solid residue in another vial was added HATU (0.091 g, 0.24 mmol), N,N-dimethylformamide (1.5 mL), triethylamine (0.18 mL, 1.28 mmol). The mixture was stirred for 10 min then O-(tert-butyldimethylsilyl)hydroxylamine (0.047 g, 0.32 mmol) in DCM (0.5 mL) was added. The solution was shaken at rt for 2 h, after which the solvent was then completely removed to afford a brown oil. To this oil in another vial was added hydrochloric acid (3.5 mL, 1% in IPA). After shaking at rt for 30 min, solid NaHCO3 was added to quench the excess acid, and the solvent was then removed. To the solid residue was added DMSO (1.2 mL). After filtration, the DMSO solution was purified by Gilson prep-HPLC to give the title compound (0.091 g, 15%) as a white solid. LC-MS: (FA) ES− 387; 1H NMR (Methanol-d4, 400 MHz) δ7.79 (d, J=8.3 Hz, 2H), 7.66 (d, J=8.3 Hz, 2H), 7.51 (d, J=8.5 Hz, 2H), 7.19 (d, J=8.5 Hz, 2H), 4.53 (q, J=7.0 Hz, 1H), 1.36 (d, J=7.0 Hz, 3H).

Workup

  1. customthe mixture was evaporated to dryness
  2. customto give a residue which
  3. stirringThe mixture was stirred for 10 min
  4. stirringThe solution was shaken at rt for 2 h
  5. customafter which the solvent was then completely removed
  6. customto afford a brown oil
  7. stirringAfter shaking at rt for 30 min
  8. customto quench the excess acid
  9. customthe solvent was then removed
  10. additionTo the solid residue was added DMSO (1.2 mL)
  11. filtrationAfter filtration
  12. customthe DMSO solution was purified by Gilson prep-HPLC

Sources & evidence

ORD record
ord-23c8d23ee009427e8482e653cb759242
Source dataset
uspto-grants-2016_07
Patent number
US09382197B2

Reaction notes

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