Oxalyl chloride → 2'-Fluoro[1,1'-biphenyl]-4-carbonyl chloride

HRID 457923Notes

Reaction equation

HRID 457923 reaction equation
CON=C1CN([C:9]([C:11]2[CH:16]=[CH:15][C:14]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=3[F:23])=[CH:13][CH:12]=2)=[O:10])[C@H](C(OC)=O)C1.FC1C=CC=CC=1C1C=CC(C(O)=O)=CC=1.C(Cl)(=O)C([Cl:47])=O>C1COCC1.CN(C=O)C>[F:23][C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][C:17]=1[C:14]1[CH:15]=[CH:16][C:11]([C:9]([Cl:47])=[O:10])=[CH:12][CH:13]=1

Participants

6

Reactant 3

HCID 65578Oxalyl chlorideHCID 7150222'-Fluoro-biphenyl-4-carboxylic acidHCID 91133146methyl (2S,4EZ)-4-(methoxyimino)-1-[(2'-fluoro[1,1'-biphenyl]-4-yl)carbonyl]-2-pyrrolidinecarboxylate

Product 1

HCID 184409072'-Fluoro[1,1'-biphenyl]-4-carbonyl chloride

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 8028TetrahydrofuranSolvent

Procedure

Method B (e.g. methyl (2S,4EZ)-4-(methoxyimino)-1-[(2′-fluoro[1,1′-biphenyl]-4-yl)carbonyl]-2-pyrrolidinecarboxylate): To a solution of 2′-fluoro[1,1′-biphenyl]-4-carboxylic acid (69 mg, 0.32 mmol.) in 9 ml THF, were added oxalyl chloride (0.09 mL, 0.99 mmol) and DMF (three drops) under ice cooling. The mixture was stirred for 2 h at rt. The solvent was removed affording the corresponding acyl chloride, 2′-fluoro[1,1′biphenyl]-4-carbonyl chloride. The latter was now dissolved in THF (7 mL) and added slowly on a 0° C. solution containing the free NH-compound from the previous step, e.g. methyl (2S,4EZ)-4-(methoxyimino)-2-pyrrolidinecarboxylate (38 mg, 0.22 mmol), and triethylamine (2eq, 0.44 mmol, 0.06 ml) in THF/DCM 1:1 mixture (12 ml). The reaction mixture was stirred overnight at r.t. Pol-trisamine was added (69 mg, 3.45 mmol/g) in order to scavenge excess of acyl chloride. The mixture was shaken 5 h, filtered and the resulting solution was washed with NH4Cl 20%, brine, and dried over MgSO4. After filtration and evaporation of the solvents, the resulting dark oil (3.26 g) was purified by SPE (SAX sorbent) using neat DCM as eluent. The desired product, e.g. methyl (2S,4EZ)-4-(methoxyimino)-1-[(2′-fluoro[1,1′-biphenyl]-4-yl)carbonyl]-2-pyrrolidinecarboxylate was obtained as a mixture of two isomers as a white foam in 34% yield (97.3% purity by HPLC).

Workup

  1. customThe solvent was removed

Sources & evidence

ORD record
ord-ca67cf3da5ae4503a3861d0e57b77e66
Source dataset
uspto-grants-2007_03
Patent number
US07189754B2

Reaction notes

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