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

HRID 348443Notes

Reaction equation

HRID 348443 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:30][CH3:31])(=[O:29])[C@H:21]([C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)[OH:22].C1CCN2C(=NCCC2)CC1>C1COCC1>[CH3:31][O:30][C:20](=[O:29])[C@@H: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:23]1[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=1

Participants

5

Reactant 3

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 643570methyl (2S)-2-hydroxy-2-phenylacetateHCID 867603842-Methanesulfinylpyrimidine-5-carboxylic acid (4-fluorophenyl)amide

Product 1

HCID 69523449(s)-[5-(4-Fluorophenylcarbamoyl)pyrimidin-2-yloxy]phenylacetic acid methyl esterYield 11%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A suspension of 2-methanesulfinylpyrimidine-5-carboxylic acid (4-fluorophenyl)amide (100 mg, 0.36 mmol) and (S)-(+)-methyl mandelate (86 mg, 0.52 mmol) in 3.6 mL of THF was treated dropwise with DBU (80 μL, 0.54 mmol) at room temperature. The reaction mixture clarified and turned yellow over the course of 5 min. The reaction was quenched after 24 hours by the addition of 5 mL 1 M HCl, followed by 25 mL of 1:1 (v:v) ethyl acetate:water. The mixture was extracted with 2×25 mL portions of ethyl acetate. The organic extracts were combined, dried using Na2SO4 and concentrated in vacuo. The crude material was dissolved in 30% (v/v)-ethyl acetate/hexanes and chromatographed through 15 g silica gel, followed by a second chromatography through 20 g silica gel. The product fractions were concentrated to yield 15 mg (11%) of the titled compound as a white solid. ESI-MS z/z 382 (MH+), 380 (M−H−).

Workup

  1. customturned yellow over the course of 5 min
  2. customThe reaction was quenched after 24 hours by the addition of 5 mL 1 M HCl
  3. extractionThe mixture was extracted with 2×25 mL portions of ethyl acetate
  4. customdried
  5. concentrationconcentrated in vacuo
  6. dissolutionThe crude material was dissolved in 30% (v/v)-ethyl acetate/hexanes
  7. customchromatographed through 15 g silica gel
  8. concentrationThe product fractions were concentrated

Sources & evidence

ORD record
ord-27b1687987f441f1a3c3d3d4e7903fa5
Source dataset
uspto-grants-2007_02
Patent number
US07176310B1

Reaction notes

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