Hydroxyamine hydrochloride → HCID 66781732, compound

HRID 1096722Notes

Reaction equation

HRID 1096722 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:9]23[CH2:14][CH:13]2[C:12](=O)[CH2:11][CH2:10]3)[CH:5]=[CH:6][C:7]=1[Cl:8].CC([O-])=O.[Na+].[NH2:21]O.Cl.[BH4-].[Na+]>CO.Cl[Ni]Cl>[ClH:1].[Cl:1][C:2]1[CH:3]=[C:4]([C:9]23[CH2:14][CH:13]2[CH:12]([NH2:21])[CH2:11][CH2:10]3)[CH:5]=[CH:6][C:7]=1[Cl:8]

Participants

7

Reactant 4

HCID 443297Hydroxyamine hydrochlorideHCID 517045Sodium AcetateHCID 4311764Sodium borohydrideHCID 66781708HCID 66781708, compound

Product 1

HCID 66781732HCID 66781732, compound

Reagents, catalysts & solvents 2

HCID 24385Nickel DichlorideCatalystHCID 887MethanolSolvent2×

Procedure

To a solution of 5-(3,4-dichlorophenyl)bicyclo[3.1.0]hexan-2-one (100 mg, 0.41 mmol) and anhydrous NaOAc (84 mg, 1.03 mmol) in anhydrous MeOH (5 mL) was added with stirring NH2OH.HCl (152.9 mg, 2.2 mmol). The resulting mixture was stirred at room temperature for 18 h. The reaction mixture was filtered and the filtrate was concentrated in vacuo. The residue, dioxime [IS THIS CORRECT?] was reconstituted in anhydrous MeOH (5 ml) and added to a suspension of anhydrous NiCl2 (116.94 mg, 0.9 mmol) in 5 ml of anhydrous MeOH with stirring. The reaction mixture was cooled to −30° C. and NaBH4 (340.5 mg, 9 mmol) was added in small portions. After completion of the addition the mixture was allowed to warm to room temperature and concentrated in vacuo. This was then basified with aqueous solution of NaOH and extracted with CH2Cl2 (3×). Organic phases were concentrated and the crude was purified by prep. HPLC. The oily product (mixture of isomers) was converted to HCl salt (50 mg, 50.4%). 1H NMR (500 MHz, DMSO-d6) δ ppm 0.79-0.95 (m, 2 H) 1.18-1.34 (m, 2 H) 1.38-1.45 (m, 1 H) 1.65-1.81 (m, 1 H) 1.83-1.92 (m, 1 H) 1.95-2.05 (m, 1 H) 6.32 (s, 2 H) 7.11-7.22 (m, 1 H) 7.23-7.38 (m, 2 H) 8.50 (broad, 1 H). 13C NMR (500 MHz, DMSO-d6) δ ppm 13.85 (s, 1 C) 14.52 (s, 1 C) 16.03 (s, 1 C) 18.45 (s, 1 C) 22.38 (s, 1 C) 23.24 (s, 1 C) 25.02 (s, 1 C) 26.22 (s, 1 C) 26.22 (s, 1 C) 27.48 (s, 1 C) 28.31 (s, 1 C) 28.51 (s, 1 C) 29.79 (s, 1 C) 29.89 (s, 1 C) 31.39 (s, 1 C) 31.99 (s, 1 C) 51.62 (s, 1 C) 52.72 (s, 1 C) 55.87 (s, 1 C) 127.88 (s, 1 C) 127.95 (s, 1 C) 128.06 (s, 1 C) 128.38 (s, 1 C) 128.60 (s, 1C) 130.15 (s, 1 C) 130.24 (s, 1 C) 131.54 (s, 1 C) 131.70 (s, 1 C) 142.26 (s, 1 C) 142.44 (s, 1 C). MS (M+1) 242.1.

Workup

  1. filtrationThe reaction mixture was filtered
  2. concentrationthe filtrate was concentrated in vacuo
  3. stirringwith stirring
  4. temperatureThe reaction mixture was cooled to −30° C.
  5. additionAfter completion of the addition the mixture
  6. temperatureto warm to room temperature
  7. concentrationconcentrated in vacuo
  8. extractionextracted with CH2Cl2 (3×)
  9. concentrationOrganic phases were concentrated
  10. customthe crude was purified by prep
  11. additionThe oily product (mixture of isomers)

Sources & evidence

ORD record
ord-e4c2e7034f124278a824744378e9b17c
Source dataset
uspto-grants-2012_03
Patent number
US08138377B2

Reaction notes

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