Reaction #155326

ord-e415676f86944507862b40899374e77f

Reaction equation

CCCOc1cc2c(c3c(=O)c(-c4ccc(OC)cc4)c[nH]c13)CCC2
8-(4-methoxyphenyl)-5-propoxy-1,2,3,6-tetrahydro-6-aza-cyclopenta[a]naphthalen-9-one
[I-].[Na+]
sodium iodide
[H-].[Na+]
sodium hydride
CC(C)(C)OP(=O)(OCCl)OC(C)(C)C
di-tert-butyl chloromethyl phosphate
CCCOc1cc2c(c3c(=O)c(-c4ccc(OC)cc4)cn(COP(=O)(OC(C)(C)C)OC(C)(C)C)c13)CCC2
di-tert-butyl 8-(4-methoxyphenyl)-9-oxo-5-propoxy-1,2,3,9-tetrahydro-6-aza-cyclopenta[a]naphthalen-6-ylmethyl phosphate
Yield 40.0%

Solvents

Conditions

Detailed conditions
See reaction.notes.procedure_details.

Workup

  1. 1
    workup.STIRRINGthe mixture was then stirred at 40° C. for 4 hours
  2. 2
    Temperaturecooled
  3. 3
    Extractionthe reaction mixture was subjected to extraction
  4. 4
    WashThe thus-obtained organic layer was washed with an aqueous saturated sodium chloride solution twice
  5. 5
    Dryingdried over anhydrous sodium sulfate
  6. 6
    Concentrationconcentrated under reduced pressure
  7. 7
    OtherThe residue was purified
  8. 8
    ConcentrationThe purified product was concentrated under reduced pressure

Procedure

To a DMF solution (10 ml) of 8-(4-methoxyphenyl)-5-propoxy-1,2,3,6-tetrahydro-6-aza-cyclopenta[a]naphthalen-9-one (400 mg, 1.15 mmol) and sodium iodide (343 mg, 2.29 mmol) was added sodium hydride (60% oil base, 74.9 mg, 1.72 mmol), and the mixture was then stirred for 10 minutes at room temperature. To the resulting mixture was added a DMF solution (20 ml) of di-tert-butyl chloromethyl phosphate (888 mg, 3.43 mmol), and the mixture was then stirred at 40° C. for 4 hours. The reaction mixture was ice-cooled, ice water was added thereto, and then the reaction mixture was subjected to extraction using ethyl acetate. The thus-obtained organic layer was washed with an aqueous saturated sodium chloride solution twice, dried over anhydrous sodium sulfate and then concentrated under reduced pressure. The residue was purified using medium pressure liquid chromatography (NH silica gel, n-hexane:ethyl acetate=100:0→0:100). The purified product was concentrated under reduced pressure, giving a white powder of di-tert-butyl 8-(4-methoxyphenyl)-9-oxo-5-propoxy-1,2,3,9-tetrahydro-6-aza-cyclopenta[a]naphthalen-6-ylmethyl phosphate (263 mg, yield: 40%).

Source

DOI: 10.6084/m9.figshare.5104873.v1Patent: USRE045108E1uspto-grants-2014_09