1,8-Diazabicyclo(5.4.0)undec-7-ene → [5-(4-Fluorophenylcarbamoyl)pyrimidin-2-yloxy]acetic acid benzyl ester

HRID 348441

Reaction equation

HRID 348441 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]([C:11]2[CH:12]=[N:13][C:14](S(C)=O)=[N:15][CH:16]=2)=[O:10])=[CH:4][CH:3]=1.[C:20]([O:24][CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)(=[O:23])[CH2:21][OH:22].CC(C)([O-])C.[K+].C1CCN2C(=NCCC2)CC1>C1COCC1.C(OCC)(=O)C.CCCCCC>[CH2:25]([O:24][C:20](=[O:23])[CH2:21][O:22][C:14]1[N:13]=[CH:12][C:11]([C:9](=[O:10])[NH:8][C:5]2[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=2)=[CH:16][N:15]=1)[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1

Participants

7

Reactant 4

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 561337Benzyl 2-hydroxyacetateHCID 23665647Potassium tert-butoxideHCID 867603842-Methanesulfinylpyrimidine-5-carboxylic acid (4-fluorophenyl)amide

Product 1

HCID 16004800[5-(4-Fluorophenylcarbamoyl)pyrimidin-2-yloxy]acetic acid benzyl esterYield 30.2%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 21226206Ethyl acetate hexaneSolvent

Procedure

To a solution of 2-methanesulfinylpyrimidine-5-carboxylic acid (4-fluorophenyl)amide (173 mg, contaminated with 10% sulfone, 0.62 mmol) in THF (6 mL) was added benzyl glycolate (128 μL, 0.90 mmol) followed by potassium tert-butoxide (1 M in THF, 0.3 mL, 0.3 mmol) and DBU (139 μL, 0.93 mmol). The solution was stirred for 5 h, diluted with 50% ethyl acetate/hexane, and passed through a plug of SiO2 followed by washing with 40% ethyl acetate/hexane. The filtrate was concentrated in vacuo, and the residue flash-chromatographed on SiO2 with 35% ethyl acetate/hexane to afford 71.5 mg (30% yield) of the titled product as a white solid. ESI-MS m/z 382 (MH+), 380 (M−H)−.

Workup

  1. washby washing with 40% ethyl acetate/hexane
  2. concentrationThe filtrate was concentrated in vacuo
  3. customthe residue flash-chromatographed on SiO2 with 35% ethyl acetate/hexane

Sources & evidence

ORD record
ord-7ec0e26be06e4a9b84a8b8362dc49978
Source dataset
uspto-grants-2007_02
Patent number
US07176310B1

Linked notes

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