Lithium Hydroxide → 5-Cyano-2-[3-methyl-2,5-dioxo-1-(3-trifluoromethyl-phenyl)-1,2,3,4,5,6,7,8-octahydro-quinazolin-4-yl]-benzoic acid

HRID 59657Notes

Reaction equation

HRID 59657 reaction equation
C[O:2][C:3](=[O:35])[C:4]1[CH:9]=[C:8]([C:10]#[N:11])[CH:7]=[CH:6][C:5]=1[CH:12]1[C:21]2[C:20](=[O:22])[CH2:19][CH2:18][CH2:17][C:16]=2[N:15]([C:23]2[CH:28]=[CH:27][CH:26]=[C:25]([C:29]([F:32])([F:31])[F:30])[CH:24]=2)[C:14](=[O:33])[N:13]1[CH3:34].[OH-].[Li+]>O1CCOCC1.O>[C:10]([C:8]1[CH:7]=[CH:6][C:5]([CH:12]2[C:21]3[C:20](=[O:22])[CH2:19][CH2:18][CH2:17][C:16]=3[N:15]([C:23]3[CH:28]=[CH:27][CH:26]=[C:25]([C:29]([F:32])([F:30])[F:31])[CH:24]=3)[C:14](=[O:33])[N:13]2[CH3:34])=[C:4]([CH:9]=1)[C:3]([OH:35])=[O:2])#[N:11]

Participants

5

Reactant 2

HCID 3939Lithium HydroxideHCID 1186921505-Cyano-2-[3-methyl-2,5-dioxo-1-(3-trifluoromethyl-phenyl)-1,2,3,4,5,6,7,8-octahydro-quinazolin-4-yl]-benzoic acid methyl ester2×

Product 1

HCID 1186921515-Cyano-2-[3-methyl-2,5-dioxo-1-(3-trifluoromethyl-phenyl)-1,2,3,4,5,6,7,8-octahydro-quinazolin-4-yl]-benzoic acid

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 312751,4-DioxaneSolvent

Procedure

5-Cyano-2-[3-methyl-2,5-dioxo-1-(3-trifluoromethyl-phenyl)-1,2,3,4,5,6,7,8-octahydro-quinazolin-4-yl]-benzoic acid methyl ester (INTERMEDIATE 24, 5.3 g, 11 mmol) and lithium hydroxide (0.78 g, 32.9 mmol) are stirred in 1.4-dioxane (90 ml) and water (30.0 mL) at room temperature for 7.5 h. The reaction mixture is diluted with water and the extracted with diethyl ether. The aqueous phase is acidified with hydrochloric acid to a pH of 2 and extracted with ethyl acetate. The ethyl acetate phase is evaporated under reduced pressure and the crude product is purified by reversed phase HPLC. Yield: 1.5 g; ESI mass spectrum [M+H]+=470; Retention time HPLC: 0.61 min (X012_S02).

Workup

  1. extractionthe extracted with diethyl ether
  2. extractionextracted with ethyl acetate
  3. customThe ethyl acetate phase is evaporated under reduced pressure
  4. customthe crude product is purified by reversed phase HPLC
  5. custom0.61 min (X012_S02)

Sources & evidence

ORD record
ord-a0e34f6d54a448c59a38ec7402a77574
Source dataset
uspto-grants-2016_09
Patent number
US09440930B2

Reaction notes

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