Sodium Iodide → Di-tert-butyl 8-(4-methoxyphenyl)-9-oxo-5-propoxy-1,2,3,9-tetrahydro-6-aza-cyclopenta[a]naphthalen-6-ylmethyl phosphate

HRID 1474532Notes

Reaction equation

HRID 1474532 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[C:18](=[O:19])[C:17]3[C:12](=[C:13]([O:23][CH2:24][CH2:25][CH3:26])[CH:14]=[C:15]4[CH2:22][CH2:21][CH2:20][C:16]4=3)[NH:11][CH:10]=2)=[CH:5][CH:4]=1.[I-].[Na+].[H-].[Na+].[P:31]([O:43][CH2:44]Cl)([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32]>CN(C=O)C>[P:31]([O:43][CH2:44][N:11]1[CH:10]=[C:9]([C:6]2[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:8][CH:7]=2)[C:18](=[O:19])[C:17]2[C:12]1=[C:13]([O:23][CH2:24][CH2:25][CH3:26])[CH:14]=[C:15]1[CH2:22][CH2:21][CH2:20][C:16]1=2)([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])([O:38][C:39]([CH3:40])([CH3:41])[CH3:42])=[O:32]

Participants

6

Reactant 4

HCID 5238Sodium IodideHCID 24758Sodium hydrideHCID 11701630Di-tert-butyl (chloromethyl) phosphateHCID 584925468-(4-Methoxyphenyl)-5-propoxy-1,2,3,6-tetrahydro-6-aza-cyclopenta[a]naphthalen-9-one

Product 1

HCID 46224418Di-tert-butyl 8-(4-methoxyphenyl)-9-oxo-5-propoxy-1,2,3,9-tetrahydro-6-aza-cyclopenta[a]naphthalen-6-ylmethyl phosphateYield 40%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

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%).

Workup

  1. stirringthe mixture was then stirred at 40° C. for 4 hours
  2. temperaturecooled
  3. extractionthe reaction mixture was subjected to extraction
  4. washThe thus-obtained organic layer was washed with an aqueous saturated sodium chloride solution twice
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified
  8. concentrationThe purified product was concentrated under reduced pressure

Sources & evidence

ORD record
ord-3b1194d3725d46eda974cff499d8a0a3
Source dataset
uspto-grants-2015_04
Patent number
US09018229B2

Reaction notes

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