Sodium Chloride → HCID 86660406, compound

HRID 1186138Notes

Reaction equation

HRID 1186138 reaction equation
[C:1]1([Li])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[F:8][C:9]1[CH:14]=[CH:13][C:12]([N+:15]([O-:17])=[O:16])=[CH:11][C:10]=1[C@:18]([NH:23][S@@:24]([C:26]([CH3:29])([CH3:28])[CH3:27])=[O:25])([CH3:22])[CH2:19][CH:20]=[O:21].[Na+].[Cl-].C(OC(=O)C)C>C1COCC1.CC(C)[O-].CC(C)[O-].CC(C)[O-].Cl[Ti+3]>[F:8][C:9]1[CH:14]=[CH:13][C:12]([N+:15]([O-:17])=[O:16])=[CH:11][C:10]=1[C@:18]([NH:23][S@@:24]([C:26]([CH3:29])([CH3:28])[CH3:27])=[O:25])([CH3:22])[CH2:19][C@H:20]([OH:21])[C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

7

Reactant 4

HCID 5234Sodium ChlorideHCID 8857Ethyl AcetateHCID 86660405HCID 86660405, compoundHCID 178506676HCID 178506676, compound

Product 1

HCID 86660406HCID 86660406, compoundYield 19.3%

Reagents, catalysts & solvents 2

HCID 11673339ChlorotitaniumtriisopropoxideCatalystHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of the chlorotitaniumtriisopropoxide (6.57 g, 25.2 mmol) in 80 mL dry THF at 0° C. was slowly added phenyllithium (2.0M solution in dibutylether, 12.6 mL, 25.2 mmol) and the mixture was stirred at 0° C. for 30 min, followed by a slow addition of a solution of (R)-2-Methyl-propane-2-sulfinic acid [(S)-1-(2-fluoro-5-nitro-phenyl)-1-methyl-3-oxo-propyl]-amide (4.2 g, 12.6 mmol) in 30 mL dry THF. The resulting reaction mixture was let to warm up to 23° C. and stirred at 23° C. for 2 h. The reaction medium was slowly poured into a stirred mixture of a saturated NaCl aqueous solution and ethylacetate, which was stirred for 15 min until precipitation occured. The suspension was filtered over celite, the filtrate was poured in a reparatory and extracted with water. The collected organic phase was dried over Na2SO4 and removal of solvent in vaccum yielded a crude yellow oil. The crude was purified by chromatography on silica using a mixture of heptane and ethylacetate which gave the desired diastereoisomer (R)-2-Methyl-propane-2-sulfinic acid [(1S,3S)-1-(2-fluoro-5-nitro-phenyl)-3-hydroxy-1-methyl-3-phenyl-propyl]-amide (1 g, 2.43 mmol, yield: 19.3%). MS (ISP): m/z=409.3 [(M+H)+] and a second diastereoisomer (R)-2-Methyl-propane-2-sulfinic acid [(1S,3R)-1-(2-fluoro-5-nitro-phenyl)-3-hydroxy-1-methyl-3-phenyl-propyl]-amide (2.6 g, 6.32 mmol, yield: 50.2%). MS (ISP):m/z=409.0 [(M+H)−].

Workup

  1. customat 0° C.
  2. customThe resulting reaction mixture
  3. temperatureto warm up to 23° C.
  4. stirringstirred at 23° C. for 2 h
  5. stirringwas stirred for 15 min until precipitation
  6. filtrationThe suspension was filtered over celite
  7. additionthe filtrate was poured in a reparatory
  8. extractionextracted with water
  9. dry with materialThe collected organic phase was dried over Na2SO4 and removal of solvent in vaccum
  10. customyielded a crude yellow oil
  11. customThe crude was purified by chromatography on silica using
  12. additiona mixture of heptane and ethylacetate which

Sources & evidence

ORD record
ord-b8fd727e20c54ca59837bb312e2051e2
Source dataset
uspto-grants-2014_03
Patent number
US08673894B2

Reaction notes

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