O-Methylhydroxylamine hydrochloride → HCID 76541144, compound

HRID 545575Notes

Reaction equation

HRID 545575 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:27]=[CH:28][CH:29]=1)[CH2:5][N:6]1[C:18]2[CH2:17][CH2:16][CH:15]([NH:19][C:20](=[O:24])[CH:21]([CH3:23])[CH3:22])[CH2:14][C:13]=2[C:12]2[C:7]1=[CH:8][CH:9]=[C:10]([CH:25]=O)[CH:11]=2.Cl.[CH3:31][O:32][NH2:33]>N1C=CC=CC=1>[F:1][C:2]1[CH:3]=[C:4]([CH:27]=[CH:28][CH:29]=1)[CH2:5][N:6]1[C:18]2[CH2:17][CH2:16][CH:15]([NH:19][C:20](=[O:24])[CH:21]([CH3:22])[CH3:23])[CH2:14][C:13]=2[C:12]2[C:7]1=[CH:8][CH:9]=[C:10]([CH:25]=[N:33][O:32][CH3:31])[CH:11]=2

Participants

4

Reactant 2

HCID 521874O-Methylhydroxylamine hydrochlorideHCID 57479603HCID 57479603, compound

Product 1

HCID 76541144HCID 76541144, compoundYield 34%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

Add N-[9-(3-fluoro-benzyl)-6-formyl-2,3,4,9-tetrahydro-1H-carbazol-3-yl]-isobutyramide (Example 197) (crude, 506 mg, 1.29 mmol) to a suspension of methoxyamine hydrochloride salt (140 mg, 1.48 mmol) and pyridine (10 mL). Stir the reaction at ambient temperature for 12 h. Remove the pyridine under vacuum and dissolve the resultant residue in ethyl acetate (100 mL). Wash with saturated aqueous copper sulfate (2×50 mL) and water (2×50 mL). Separate the organic layer and dry over magnesium sulfate, filter, and concentrate under vacuum to give a greasy yellow solid. The solid was purified with column chromatography (silica gel; 10% to 50% ethyl acetate in hexanes) to give 183 mg (34%) of the title compound as a white solid. mp: 180-182° C.; ESI MS m/z 422 [C25H28FN3O2+H]+; 1H NMR (300 MHz, CDCl3) δ 8.28 (s, 1H), 7.79 (s, 1H), 7.45 (d, J=7.9 Hz, 1H), 7.26-7.17 (m, 2H), 6.93 (t, J=7.1 Hz, 1H), 6.75 (d, J=7.6 Hz, 1H), 6.62 (d, J=9.1 Hz, 1H), 5.49 (br d, J=7.0 Hz, 1H), 5.24 (s, 2H), 4.40 (br s, 1H), 3.97 (s, 3H), 3.15 (dd, J=15.8, 4.7 Hz, 1H), 2.71-2.61 (m, 3H), 2.28 (septet, J=6.8 Hz, 1H), 2.07-2.00 (m, 2H), 1.14 (d, J=6.7 Hz, 3H), 1.12 (d, J=6.7 Hz, 3H).

Workup

  1. customthe reaction at ambient temperature for 12 h
  2. customRemove the pyridine under vacuum
  3. dissolutiondissolve the resultant residue in ethyl acetate (100 mL)
  4. washWash with saturated aqueous copper sulfate (2×50 mL) and water (2×50 mL)
  5. customSeparate the organic layer
  6. dry with materialdry over magnesium sulfate
  7. filtrationfilter
  8. concentrationconcentrate under vacuum
  9. customto give a greasy yellow solid
  10. customThe solid was purified with column chromatography (silica gel; 10% to 50% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-96fba683c2a74052b4d750fb58877ca2
Source dataset
uspto-grants-2011_05
Patent number
US07935722B2

Reaction notes

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