Triphenylphosphine → Cyclopropyl-(2,4,6-trichloro-pyrimidin-5-yloxy)-acetic acid methyl ester

HRID 528472Notes

Reaction equation

HRID 528472 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([Cl:8])[C:5]([OH:9])=[C:4]([Cl:10])[N:3]=1.[CH3:11][O:12][C:13](=[O:19])[CH:14]([CH:16]1[CH2:18][CH2:17]1)O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C>C1COCC1.O1CCOCC1>[CH3:11][O:12][C:13](=[O:19])[CH:14]([CH:16]1[CH2:18][CH2:17]1)[O:9][C:5]1[C:4]([Cl:10])=[N:3][C:2]([Cl:1])=[N:7][C:6]=1[Cl:8]

Participants

7

Reactant 4

HCID 11776TriphenylphosphineHCID 5363146Diisopropyl azodicarboxylateHCID 11073449Methyl cyclopropyl(hydroxy)acetateHCID 866673322,4,6-Trichloropyrimidin-5-ol

Product 1

HCID 86711755Cyclopropyl-(2,4,6-trichloro-pyrimidin-5-yloxy)-acetic acid methyl esterYield 57.5%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 312751,4-DioxaneSolvent

Procedure

To a solution of 2,4,6-trichloro-pyrimidin-5-ol (250 mg, 1.25 mmol), cyclopropyl-hydroxy-acetic acid methyl ester (245 mg, 1.88 mmol) and triphenylphosphine (493 mg, 1.88 mmol) in THF (12 mL) was added DIAD (370 μL, 1.88 mmol) dropwise. The resultant suspension was stirred for 18 hours before the addition of dioxane (10 mL) and the reaction stirred for a further 6 hours. The heterogeneous mixture was concentrated in vacuo and the resultant residue was purified by column chromatography (SiO2, gradient 0-30% ethyl acetate in cyclohexane) affording Cyclopropyl-(2,4,6-trichloro-pyrimidin-5-yloxy)-acetic acid methyl ester as a white solid (224 mg, 32%). LCMS: RT=3.66 min, [M+H]+=311/313/315.

Workup

  1. concentrationThe heterogeneous mixture was concentrated in vacuo
  2. customthe resultant residue was purified by column chromatography (SiO2, gradient 0-30% ethyl acetate in cyclohexane)

Sources & evidence

ORD record
ord-986524a5aa5f4d1383a7256040e8fce9
Source dataset
uspto-grants-2016_05
Patent number
US09346817B2

Reaction notes

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