Triphenylphosphine → [2-(2,5-Dichloro-pyrimidin-4-ylamino)-3-fluoro-phenoxy]-acetic acid methyl ester

HRID 1041704Notes

Reaction equation

HRID 1041704 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([NH:8][C:9]2[C:14]([F:15])=[CH:13][CH:12]=[CH:11][C:10]=2[OH:16])[C:5]([Cl:17])=[CH:4][N:3]=1.[C:18]([O:22][CH3:23])(=[O:21])[CH2:19]O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)(C)C)=O)=NC(OC(C)(C)C)=O>C(Cl)Cl>[CH3:23][O:22][C:18](=[O:21])[CH2:19][O:16][C:10]1[CH:11]=[CH:12][CH:13]=[C:14]([F:15])[C:9]=1[NH:8][C:6]1[C:5]([Cl:17])=[CH:4][N:3]=[C:2]([Cl:1])[N:7]=1

Participants

6

Reactant 4

HCID 11776Triphenylphosphine2×HCID 66774Methyl Glycolate2×HCID 97268Di-tert-butyl azodicarboxylate2×HCID 866339952-(2,5-Dichloro-pyrimidin-4-ylamino)-3-fluoro-phenol

Product 1

HCID 86634068[2-(2,5-Dichloro-pyrimidin-4-ylamino)-3-fluoro-phenoxy]-acetic acid methyl esterYield 79.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a suspension of 2-(2,5-Dichloro-pyrimidin-4-ylamino)-3-fluoro-phenol (0.300 g, 1.09 mmol), Methyl Glycolate (0.118 g, 1.31 mmol), and Triphenylphosphine (0.459 g, 1.75 mmol) in Methylene chloride (10 mL) cooled to 0° C. on an ice bath was slowly added Di-tert-butyl azodicarboxylate (0.403 g, 1.75 mmol), at which time a solution formed. The reaction mixture was stirred at rt overnight. The reaction did not go to completion, so one additional equivalent of Methyl Glycolate and Triphenylphosphine were added to the reaction mixture, which was then cooled to 0° C. and one equivalent of Di-tert-butyl azodicarboxylate was also added. The reaction was stirred at rt for an hour. The reaction mixture was concentrated and dissolved in minimal amounts of DCM. It was then purified by silica gel chromatography in 0-50% ethyl acetate solvent to afford [2-(2,5-Dichloro-pyrimidin-4-ylamino)-3-fluoro-phenoxy]-acetic acid methyl ester as a clear oil (0.30 g, 79%). 1H-NMR (DMSO): 9.26 (s, 1H), 8.37 (s, 1H), 7.34 (m, 1H), 6.98 (m, 2H), 4.83 (s, 2H), 3.66 (s, 3H).

Workup

  1. customat which time a solution formed
  2. additionwere added to the reaction mixture, which
  3. temperaturewas then cooled to 0° C.
  4. stirringThe reaction was stirred at rt for an hour
  5. concentrationThe reaction mixture was concentrated
  6. dissolutiondissolved in minimal amounts of DCM
  7. customIt was then purified by silica gel chromatography in 0-50% ethyl acetate solvent

Sources & evidence

ORD record
ord-bb9665cc84dc492eada4e4f4904e3a81
Source dataset
uspto-grants-2013_10
Patent number
US08552186B2

Reaction notes

Loading…