Hydrochloric Acid → HCID 10139892, compound

HRID 967120Notes

Reaction equation

HRID 967120 reaction equation
C[O:2][C:3]([C:5]1[CH:6]=[C:7]([C:11]2[CH:16]=[CH:15][C:14]([CH2:17][NH:18][C:19]([C:21]3[C:22]([O:27][C:28]4[CH:33]=[CH:32][CH:31]=[C:30]([C:34]#[N:35])[CH:29]=4)=[N:23][CH:24]=[CH:25][CH:26]=3)=[O:20])=[C:13]([F:36])[CH:12]=2)[CH:8]=[CH:9][CH:10]=1)=[O:4].[Li+].[OH-].Cl.CO.ClCCl>O1CCCC1.O>[C:34]([C:30]1[CH:29]=[C:28]([CH:33]=[CH:32][CH:31]=1)[O:27][C:22]1[C:21]([C:19]([NH:18][CH2:17][C:14]2[CH:15]=[CH:16][C:11]([C:7]3[CH:8]=[CH:9][CH:10]=[C:5]([C:3]([OH:4])=[O:2])[CH:6]=3)=[CH:12][C:13]=2[F:36])=[O:20])=[CH:26][CH:25]=[CH:24][N:23]=1)#[N:35]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 20601401HCID 20601401, compoundHCID 21226129Dichloromethane methanol

Product 1

HCID 10139892HCID 10139892, compoundYield 85.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 336 mg (0.7 mmol.) 4′-[[[2-[3-Cyano-phenoxy]-pyridine-3-carbonyl]-amino]-methyl]-3′-fluoro-biphenyl-3-carboxylic acid methyl ester and 0.8 mL (0.8 mmol.) 1.0 N LiOH in 20 mL tetrahydrofuran and 2 mL water was stirred at ambient temperature for 18 hours. The mixture was poured into water, acidified to pH 1 with 1N HCl, then extracted with ethyl acetate. The ethyl acetate extracts were combined, washed successively with water, brine then dried (MgSO4) and concentrated in vacuo to give a solid. Chromatography on Silica Gel eluting with methanol/dichloromethane (1:20) yielded a solid. Recrystallization from ethyl acetate/hexane afforded 280 mg 4′-[[[2-[3-cyano-phenoxy]-pyridine-3-carbonyl]-amino]-methyl]-3′-fluoro-biphenyl-3-carboxylic acid as a solid, mp 200-2° C.

Workup

  1. extractionextracted with ethyl acetate
  2. washwashed successively with water, brine
  3. dry with materialthen dried (MgSO4)
  4. concentrationconcentrated in vacuo
  5. customto give a solid
  6. customRecrystallization from ethyl acetate/hexane

Sources & evidence

ORD record
ord-75021dcfe426473c90289597e025500b
Source dataset
uspto-grants-2005_10
Patent number
US06953810B2

Reaction notes

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