Cesium carbonate → HCID 69199557, compound

HRID 1823232Notes

Reaction equation

HRID 1823232 reaction equation
[CH2:1]([O:3][C:4]([CH:6]([O:8][C:9](=[O:31])[C@H:10]([C:24]1[CH:25]=[C:26]([CH3:30])[CH:27]=[CH:28][CH:29]=1)[CH2:11][C:12]#[C:13][C:14]([C:16]1[CH:21]=[CH:20][C:19]([Cl:22])=[C:18]([Cl:23])[CH:17]=1)=O)[CH3:7])=[O:5])[CH3:2].C([O-])([O-])=O.[Cs+].[Cs+].Cl.[CH3:39][O:40][C:41]1[CH:46]=[CH:45][C:44]([NH:47][NH2:48])=[CH:43][CH:42]=1>C1COCC1>[CH2:1]([O:3][C:4]([CH:6]([O:8][C:9](=[O:31])[C@H:10]([C:24]1[CH:25]=[C:26]([CH3:30])[CH:27]=[CH:28][CH:29]=1)[CH2:11][C:12]1[CH:13]=[C:14]([C:16]2[CH:21]=[CH:20][C:19]([Cl:22])=[C:18]([Cl:23])[CH:17]=2)[N:47]([C:44]2[CH:45]=[CH:46][C:41]([O:40][CH3:39])=[CH:42][CH:43]=2)[N:48]=1)[CH3:7])=[O:5])[CH3:2]

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 27239044-Methoxyphenylhydrazine hydrochlorideHCID 11583465HCID 11583465, compound

Product 1

HCID 69199557HCID 69199557, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of (S)-6-(3,4-dichloro-phenyl)-6-oxo-2-m-tolyl-hex-4-ynoic acid 1-ethoxycarbonyl-ethyl ester from Example 502 (15.5 g, 0.0336 mol) in THF (150 mL) was added Cs2CO3 (8.8 g, 0.027 mol) followed by 4-methoxyphenyl hydrazine HCl (6.5 g, 0.037 mol). The resulting slurry was stirred at rt overnight and then slowly quenched with 1 N HCl until pH 2-3. The mixture was transferred to a separatory funnel and extracted with EtOAc (3×75 mL). The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated to an oil. The crude oil was purified by pad filtration on silica gel using EtOAc/hexanes to obtain the pyrazole as mixture of two regioisomers in 4:1 ratio (18.6 g, 95%). Chiral HPLC (Method S): Rt (R,S)=5.6 min; (S,S)=6.3 min. 1H NMR (400 MHz, CDCl3): 7.31-7.07 (m, 8H), 6.91-6.86 (m, 3H), 6.23 (s, 1H), 5.13 (dd, J=10.4, 7.0 Hz, 1H), 4.16 (m, 1H), 4.07 (dd, J=14.4, 7.2 Hz, 2H), 3.82 (s, 3H), 3.51 (dd, J=14.9, 9.6 1H), 3.04 (dd, J=14.9, 6.3 Hz, 1H), 2.37 (s, 3H), 1.42 (d, J=7.0 Hz, 3H), 1.12 (t, J=7.3 Hz, 3H).

Workup

  1. customslowly quenched with 1 N HCl until pH 2-3
  2. customThe mixture was transferred to a separatory funnel
  3. extractionextracted with EtOAc (3×75 mL)
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated to an oil
  8. filtrationThe crude oil was purified by pad filtration on silica gel

Sources & evidence

ORD record
ord-f24759da1872414f8deee696601e66f3
Source dataset
uspto-grants-2006_05
Patent number
US07037931B2

Reaction notes

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