Hydroxylamine → HCID 11414703, compound

HRID 545494Notes

Reaction equation

HRID 545494 reaction equation
C[O:2][C:3]([C:5]1[S:6][C:7]([NH:10][C:11](=[O:19])[CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[CH:8][CH:9]=1)=O.NO.Cl.C[O-].[Na+].C(N(C(C)C)CC)(C)C.CN(C([O:42][N:43]1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.NO>O.CO>[OH:42][NH:43][C:3]([C:5]1[S:6][C:7]([NH:10][C:11](=[O:19])[CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[CH:8][CH:9]=1)=[O:2]

Participants

9

Reactant 6

HCID 787HydroxylamineHCID 81531DiisopropylethylamineHCID 443297Hydroxyamine hydrochlorideHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 10942334Sodium Methoxide2×HCID 67200997HCID 67200997, compound

Product 1

HCID 11414703HCID 11414703, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

To 5-phenylacetylamino-thiophene-2-carboxylic acid methyl ester (92.7 mg, 0.34 mmol) were added NH2OH.HCl (110.0 mg, 1.58 mmol) and 5 mL of anhydrous MeOH. A solution of NaOMe (4.37 M in MeOH, 0.75 mL, 3.28 mmol) was added. The resulting mixture was allowed to stir at 50° C. for 6 h, at ii for 14 h, again at 50° C. for 3 days and then at rt for additional 2 days. Five mL of water was added and the mixture was stirred at rt for 3 days. A solution of NaOMe (4.37 M in MeOH, 0.75 mL, 3.28 mmol) was then added and the resulting mixture was allowed to stir at rt for additional 3 days. After the reaction was complete, MeOH was removed and the aqueous layer was acidified with 2N aqueous HCl to pH≈2. After extracted with 2×15 mL of EtOAc, the combined organic layer was concentrated and dried under high vacuum. The residue was subsequently dissolved in 6 mL of anhydrous DMF and the mixture was cooled to 0° C. Diisopropylethylamine (0.20 mL, 1.15 mmol) and HBTU (210.7 mg, 0.56 mmol) were added. After stirring at 0° C. for 1 h and at it for additional 1 h, 1.3 mL of 50% aqueous NH2OH solution was added and the mixture was allowed to stir at rt overnight. After concentration under high vacuum, the resulting residue was purified by flash column chromatography (70% EtOAc/hexanes to EtOAc and then to 10% MeOH/EtOAc) to give 5-phenylacetylamino-thiophene-2-carboxylic acid hydroxyamide as a pale solid. 1H NMR (DMSO-d6, 200 MHz) δ 7.55-7.15 (m, 6H), 6.64 (d, J=4.0 Hz, 1H), 3.68 (s, 2H). MS (EI): cal'd 277.31 (MH+), exp 277.25 (MH+).

Workup

  1. stirringto stir at rt for additional 3 days
  2. customMeOH was removed
  3. extractionAfter extracted with 2×15 mL of EtOAc
  4. concentrationthe combined organic layer was concentrated
  5. customdried under high vacuum
  6. dissolutionThe residue was subsequently dissolved in 6 mL of anhydrous DMF
  7. temperaturethe mixture was cooled to 0° C
  8. stirringAfter stirring at 0° C. for 1 h and at it for additional 1 h
  9. stirringto stir at rt overnight
  10. concentrationAfter concentration under high vacuum
  11. customthe resulting residue was purified by flash column chromatography (70% EtOAc/hexanes to EtOAc

Sources & evidence

ORD record
ord-3d05bbf878d846c88ef12b1420d4c418
Source dataset
uspto-grants-2011_05
Patent number
US07935724B2

Reaction notes

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