Tributylphosphine → HCID 178470442, compound

HRID 1168195Notes

Reaction equation

HRID 1168195 reaction equation
P(CCCC)(CCCC)CCCC.[N+:14](=[C:16]([C:22]([C:24]1[CH:29]=[C:28]([CH2:30][N:31]2[CH2:36][CH2:35][O:34][CH2:33][CH2:32]2)[CH:27]=[CH:26][C:25]=1F)=[O:23])[C:17]([O:19][CH2:20][CH3:21])=[O:18])=[N-:15]>O1CCOCC1>[OH:23][C:22]1[C:24]2[C:25](=[CH:26][CH:27]=[C:28]([CH2:30][N:31]3[CH2:36][CH2:35][O:34][CH2:33][CH2:32]3)[CH:29]=2)[N:15]=[N:14][C:16]=1[C:17]([O:19][CH2:20][CH3:21])=[O:18]

Participants

4

Reactant 2

HCID 13831TributylphosphineHCID 72594823HCID 72594823, compound

Product 1

HCID 178470442HCID 178470442, compoundYield 6.7%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent2×

Procedure

A solution of Bu3P (3.90 mL) in dioxane (20 mL) is added to a stirred solution of ethyl 2-diazo-3-[2-fluoro-5-(4-morpholinylmethyl)phenyl]-3-oxopropanoate (Preparation 10, 3.16 g) in dry dioxane (56 mL). The mixture is stirred at room temperature for 30 min then gently refluxed for 1.5 h. The reaction is cooled and concentrated. The crude product is purified by column chromatography (CH2Cl2/MeOH, 99/1; CH2Cl2/MeOH, 98/2; CH2Cl2/MeOH, 95/5) to yield 0.200 g of the desired product as an off-white solid. Additional material can be obtained by heating the acyclic intermediate which is isolated in the chromatography at 130° C. in diglyme (32 mL) for 3.5 h. The resulting mixture is concentrated. The crude product is purified by column chromatography (CH2Cl2/MeOH, 99/1; CH2Cl2/MeOH, 98/2; CH2Cl2/MeOH, 95/5) to yield 0.531 g of the desired product. Retreatment the unreacted starting material from the first step to Bu3P (dioxane, reflux, 5 h), chromatography, and cyclization of the uncyclized product as above (diglyme, 3.5 h) provides an additional 1.06 g of the desired product to give an overall yield of 1.79 g (40%). Physical characteristics are as follows: m.p. 195-197° C. (dec); 1H NMR (DMSO-d6) δ14.0, 8.01, 7.83, 7.67, 4.30, 3.60, 2.38, 1.30; MS (ESI−) for C16H19N3O m/z 316 (M−H)−.

Workup

  1. temperaturethen gently refluxed for 1.5 h
  2. temperatureThe reaction is cooled
  3. concentrationconcentrated
  4. customThe crude product is purified by column chromatography (CH2Cl2/MeOH, 99/1; CH2Cl2/MeOH, 98/2; CH2Cl2/MeOH, 95/5)

Sources & evidence

ORD record
ord-cc60857f18544221aef6f71a9438e7ea
Source dataset
uspto-grants-2003_09
Patent number
US06624160B2

Reaction notes

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