Phenylhydrazine hydrochloride → HCID 11852744, compound

HRID 1880577Notes

Reaction equation

HRID 1880577 reaction equation
O=[CH:2][CH2:3][CH:4]([C:24]1[CH:25]=[C:26]([C:30]2[CH:35]=[CH:34][C:33]([O:36][C:37]([F:40])([F:39])[F:38])=[CH:32][CH:31]=2)[CH:27]=[CH:28][CH:29]=1)[CH2:5][C:6]1[CH:23]=[CH:22][C:9]([C:10]([NH:12][CH2:13][CH2:14][C:15]([O:17]C(C)(C)C)=[O:16])=[O:11])=[CH:8][CH:7]=1.Cl.[C:42]1([NH:48]N)[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1>[Cl-].[Cl-].[Zn+2].C(O)(=O)C>[NH:48]1[C:42]2[C:43](=[CH:44][CH:45]=[CH:46][CH:47]=2)[C:3]([CH:4]([C:24]2[CH:25]=[C:26]([C:30]3[CH:31]=[CH:32][C:33]([O:36][C:37]([F:38])([F:39])[F:40])=[CH:34][CH:35]=3)[CH:27]=[CH:28][CH:29]=2)[CH2:5][C:6]2[CH:7]=[CH:8][C:9]([C:10]([NH:12][CH2:13][CH2:14][C:15]([OH:17])=[O:16])=[O:11])=[CH:22][CH:23]=2)=[CH:2]1

Participants

5

Reactant 2

HCID 60962Phenylhydrazine hydrochlorideHCID 86761703HCID 86761703, compound

Product 1

HCID 11852744HCID 11852744, compound

Reagents, catalysts & solvents 2

HCID 3007855ZincchlorideCatalystHCID 176Acetic AcidSolvent

Conditions

Temperature
80 °C

Procedure

A glacial acetic acid solution (4 mL) containing the intermediate from Step C (150 mg, 0.27 mmol), phenyl hydrazine hydrochloride (51 mg, 0.35 mmol) and ZnCl2 (110 mg, 0.81 mmol) was heated at 80° C. for 1 hour. The solution was concentrated and partitioned between aqueous 1N HCl and ethyl acetate. The organic phase was washed with brine, dried over MgSO4, filtered and concentrated. The residue was purified by RP-HPLC and the isolated material was resolved using chiral OJ SFC-HPLC to give the title compounds. Isomer A: Chiral LC1 4.85 min, LCMS1 3.80 min. (M+H)=572. Isomer B: Chiral LC1 12.09 min, LCMS1 3.80 min. (M+H)=572. Representative 1H NMR (400 MHz, CD3OD): δ 7.58 (d, J=8.2 Hz, 2H); 7.47 (d, J=8.6 Hz, 2H); 7.37-7.14 (m, 11H); 7.01 (t, J=7.5 Hz, 1H); 6.85 (t, J=7.5 Hz, 1H); 4.57 (t, J=7.9 Hz, 1H); 3.63 (dd, J=6.7, 13.4 Hz, 1H); 3.56 (t, J=6.9 Hz, 2H); 3.36 (dd, J=9.1, 13.3 Hz, 1H); 2.57 (t, J=7.0 Hz, 2H).

Workup

  1. concentrationThe solution was concentrated
  2. custompartitioned between aqueous 1N HCl and ethyl acetate
  3. washThe organic phase was washed with brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by RP-HPLC

Sources & evidence

ORD record
ord-8e436370929a4f32baac6ec260f45815
Source dataset
uspto-grants-2012_11
Patent number
US08318760B2

Reaction notes

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