Hydroxylamine → HCID 71748115, compound

HRID 2277087Notes

Reaction equation

HRID 2277087 reaction equation
C([O-])([O-])=O.[K+].[K+].C([O:10][C@H:11]([C:40]([CH3:43])([CH3:42])[CH3:41])[C:12]([N:14]1[CH2:19][CH2:18][CH2:17][CH2:16][C@H:15]1[C:20](=[O:39])[NH:21][CH2:22][C:23]1[CH:28]=[C:27]([Cl:29])[CH:26]=[CH:25][C:24]=1[CH2:30][NH:31]C(OC(C)(C)C)=O)=[O:13])(=O)C.NO.[F:46][C:47]([F:52])([F:51])[C:48]([OH:50])=[O:49]>CO.CCOC(C)=O.C(Cl)Cl>[F:46][C:47]([F:52])([F:51])[C:48]([OH:50])=[O:49].[NH2:31][CH2:30][C:24]1[CH:25]=[CH:26][C:27]([Cl:29])=[CH:28][C:23]=1[CH2:22][NH:21][C:20]([C@@H:15]1[CH2:16][CH2:17][CH2:18][CH2:19][N:14]1[C:12](=[O:13])[C@H:11]([OH:10])[C:40]([CH3:43])([CH3:42])[CH3:41])=[O:39]

Participants

8

Reactant 4

HCID 787HydroxylamineHCID 6422Trifluoroacetic acidHCID 11430Potassium CarbonateHCID 89824779HCID 89824779, compound

Product 1

HCID 71748115HCID 71748115, compound

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

Solid K2CO3 (7.5 mg, 0.052 mmol) was added to a solution of (R)-1-{(S)-2-[2-{(tert-butoxycarbonylamino)methyl}-5-chlorobenzylcarbamoyl]-piperidin-1-yl}-3,3-dimethyl-1-oxobutan-2-yl acetate (0.14 g, 0.26 mmol) in MeOH (5 mL) and the resulting mixture was stirred at room temperature for 30 min. The reaction mixture was diluted with EtOAc (50 mL) and washed sequentially with 0.1 N aqueous HCl (20 mL), water (2×20 mL), and brine solution (20 mL). The organic layer was dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by reverse phase combiflash column chromatography (C18; eluent: 10-100% acetonitrile/water) to provide the intermediate BOC protected amino alcohol (0.12 g, crude) as an off-white solid. The crude intermediate was dissolved in CH2Cl2 (2 mL) then trifluoroacetic acid (0.5 mL, 27.20 mmol) was added. The reaction mixture was stirred at room temperature for 2 h then volatile byproducts were removed under reduced pressure residue. The residue was purified by reverse phase combiflash column chromatography (C18; eluent: 10-100% acetonitrile:water) to afford the title compound as a white solid. 1H NMR (MeOD, 400 MHz) (δ) ppm: 7.36-7.46 (m, 3H), 4.99-5.08 (m, 1H), 4.01-4.51 (m, 6H), 3.36-3.37 (m, 1H), 2.15-2.21 (m, 1H), 1.64-1.68 (m, 3H), 1.39-1.54 (m, 2H), 0.98 (s, 9H).

Workup

  1. washwashed sequentially with 0.1 N aqueous HCl (20 mL), water (2×20 mL), and brine solution (20 mL)
  2. dry with materialThe organic layer was dried over anhydrous Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by reverse phase combiflash column chromatography (C18; eluent: 10-100% acetonitrile/water)
  6. customto provide the intermediate BOC
  7. stirringThe reaction mixture was stirred at room temperature for 2 h
  8. customvolatile byproducts were removed under reduced pressure residue
  9. customThe residue was purified by reverse phase combiflash column chromatography (C18; eluent: 10-100% acetonitrile:water)

Sources & evidence

ORD record
ord-7abf094dfefb4c23a9d15736a71a68e6
Source dataset
uspto-grants-2015_09
Patent number
US09133147B2

Reaction notes

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