Hydrazine hydrate (1:1) → HCID 178440965, compound

HRID 1879623Notes

Reaction equation

HRID 1879623 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([CH:20]([C:24]2[CH:41]=[CH:40][C:27]([C:28]([NH:30][CH2:31][CH2:32][C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])=[O:29])=[CH:26][CH:25]=2)[CH2:21][CH2:22][CH3:23])[C:9]([C:11]2[CH:16]=[C:15]([Cl:17])[CH:14]=[C:13]([CH3:18])[C:12]=2Cl)=O)=[CH:4][CH:3]=1.O.[NH2:43][NH2:44]>CS(C)=O.[Na+].[Cl-]>[Cl:17][C:15]1[CH:16]=[C:11]2[C:12](=[C:13]([CH3:18])[CH:14]=1)[NH:44][N:43]=[C:9]2[CH:8]([C:5]1[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=1)[CH:20]([C:24]1[CH:25]=[CH:26][C:27]([C:28]([NH:30][CH2:31][CH2:32][C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])=[O:29])=[CH:40][CH:41]=1)[CH2:21][CH2:22][CH3:23]

Participants

5

Reactant 2

HCID 24654Hydrazine hydrate (1:1)HCID 58538050HCID 58538050, compound

Product 1

HCID 178440965HCID 178440965, compound

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 5234Sodium ChlorideSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of the major diastereomer of the product of Step A (271 mg, 0.439 mmol) in DMSO (25 mL) was added hydrazine hydrate (60 wt %, 0.90 mL, 11 mmol). The mixture was stirred at 100° C. for two days in a sealed tube. The mixture was diluted with saturated NaCl (aq) then extracted twice with ethyl acetate. The combined organic layers were then washed with 2 N HCl (aq), saturated NaHCO3 (aq), and saturated NaCl (aq). The organic layer was dried over sodium sulfate, filtered, then concentrated. The resulting residue was purified by silica gel chromatography eluting with 0-50% EtOAc/hexanes to afford the major diastereomer of the title compound as a solid. This diastereomer was resolved to provide enantiopure material by supercritical fluid chromatography on a ChiralPak OJ-H column (2 cm×25 cm) eluting with 50 mL/min of 20% (MeOH+0.1% Et2NH) and 80% CO2 at 35° C. and 100 bar. LC1 2.58 min. (M-tBu+H)+ 538.

Workup

  1. extractionthen extracted twice with ethyl acetate
  2. washThe combined organic layers were then washed with 2 N HCl (aq), saturated NaHCO3 (aq), and saturated NaCl (aq)
  3. dry with materialThe organic layer was dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe resulting residue was purified by silica gel chromatography
  7. washeluting with 0-50% EtOAc/hexanes

Sources & evidence

ORD record
ord-84074ea8ce8142559477b8e4f52d0fbe
Source dataset
uspto-grants-2012_11
Patent number
US08318667B2

Reaction notes

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