Ammonia → Boc-serinol ketoprofen

HRID 1359992Notes

Reaction equation

HRID 1359992 reaction equation
[OH:1][C:2]([CH:4]([C:6]1[CH:19]=[CH:18][CH:17]=[C:8]([C:9]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=[O:10])[CH:7]=1)[CH3:5])=[O:3].C(N(CC)CC)C.CP(Cl)(C)=S.[C:32]([NH:39][CH:40]([CH2:43][OH:44])[CH2:41][OH:42])([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33].NC(O)CC.CC(NC1C=CC(CC(O)=O)=CC=1)=O.Cl.N>ClCCl.CN(C1C=CN=CC=1)C.O1CCOCC1>[C:32]([NH:39][CH:40]([CH2:41][OH:42])[CH2:43][OH:44])([O:34][C:35]([CH3:37])([CH3:38])[CH3:36])=[O:33].[OH:3][C:2]([CH:4]([C:6]1[CH:19]=[CH:18][CH:17]=[C:8]([C:9]([C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=2)=[O:10])[CH:7]=1)[CH3:5])=[O:1]

Participants

10

Reactant 6

HCID 222AmmoniaHCID 3825KetoprofenHCID 8471Triethylamine3×HCID 61245Phosphinothioic chloride, dimethyl-HCID 10631565N-Boc-serinolHCID 86623044HCID 86623044, compound

Product 1

HCID 86623045Boc-serinol ketoprofenYield 87%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×HCID 312751,4-DioxaneSolvent

Procedure

Ketoprofen (1.11 mmol) (manufactured by Tokyo Kasei Kogyo) was dissolved in dichloromethane (3 ml), and triethylamine (1.11 mmol) and dichloromethane solution (2 ml) of dimethylphosphinothioyl chloride (Mpt-Cl) (1.11 mmol) were added thereto in this order, followed by stirring for 25 minutes. Triethylamine (0.36 mmol) was further added thereto, followed by stirring for 20 minutes. The reaction solution was ice-cooled, and triethylamine (1.11 mmol), DMAP (0.19 mmol) and the Boc-serinol obtained in Reference Example 2 (0.50 mmol) were added thereto in this order, followed by stirring overnight by returning to room temperature. The reaction solution was again ice-cooled, and 25% aqueous ammonia (2 ml) and dioxane (10 ml) were added thereto in this order, followed by stirring for 20 minutes. The reaction solution was concentrated to 5 ml, and ethyl acetate was added thereto. Separation by washing with water, 5% aqueous citric acid solution, 5% aqueous sodium hydrogen carbonate solution and saturated brine consecutively was carried out, and after dehydration drying with sodium sulfate the solvent was evaporated under reduced pressure. The precipitate was purified by silica gel column chromatography (hexane:ethyl acetate=2:1, 0.5% triethylamine) to give the titled compound (287.3 mg, yield 87%). The structure was identified by 1H-NMR (CDCl3).

Workup

  1. stirringby stirring for 20 minutes
  2. temperaturecooled
  3. additionwere added
  4. stirringby stirring overnight
  5. customby returning to room temperature
  6. temperaturecooled
  7. stirringby stirring for 20 minutes
  8. concentrationThe reaction solution was concentrated to 5 ml, and ethyl acetate
  9. additionwas added
  10. customSeparation
  11. washby washing with water, 5% aqueous citric acid solution, 5% aqueous sodium hydrogen carbonate solution and saturated brine
  12. dry with materialafter dehydration drying with sodium sulfate the solvent
  13. customwas evaporated under reduced pressure
  14. customThe precipitate was purified by silica gel column chromatography (hexane:ethyl acetate=2:1, 0.5% triethylamine)

Sources & evidence

ORD record
ord-c3ea5eb7d86b4d3192ad6b5d52bb52cb
Source dataset
uspto-grants-2011_02
Patent number
US07879817B2

Reaction notes

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