Sulfuric Acid → 2-Fluoro-5-(4-oxo-3,4,5,6,7,8-hexahydro-phthalazin-1-ylmethyl)-benzoic acid

HRID 1012955Notes

Reaction equation

[F:1][C:2]1[CH:9]=[CH:8][C:7]([CH2:10][C:11]2[C:20]3[CH2:19][CH2:18][CH2:17][CH2:16][C:15]=3[C:14](=[O:21])[NH:13][N:12]=2)=[CH:6][C:3]=1[C:4]#N.[OH-:22].[Na+].S(=O)(=O)(O)[OH:25]>O>[F:1][C:2]1[CH:9]=[CH:8][C:7]([CH2:10][C:11]2[C:20]3[CH2:19][CH2:18][CH2:17][CH2:16][C:15]=3[C:14](=[O:21])[NH:13][N:12]=2)=[CH:6][C:3]=1[C:4]([OH:25])=[O:22]

Participants

Conditions

Temperature: 60 °C

Procedure

Crude 2-fluoro-5-(4-oxo-3,4,5,6,7,8-hexahydrophthalazin-1-ylmethyl)benzonitrile (10) (9.9 g, 34.9 mmol) was suspended in water (245 ml) and treated with sodium hydroxide (6.98 g, 174 mmol). The mixture was heated to 60° C. for 18 hours. The reaction was then cooled to 5° C. and concentrated sulfuric acid added dropwise until a precipitate formed (ca 10 ml, pH2). The suspension was stirred for 10 minutes at 5° C. and filtered. The solid isolated was washed with water (2×8 ml) and triturated with DCM (20 ml) before being dried. Single peak in LC-MS, (4.48 g, 98% purity) and was taken through to the next without any further purification; m/z (LC-MS, ESN), RT=1.96 mins (M−H 301.3).

Workup

temperatureThe reaction was then cooled to 5° C.
customformed (ca 10 ml, pH2)
filtrationfiltered
customThe solid isolated
washwas washed with water (2×8 ml)
customtriturated with DCM (20 ml)
custombefore being dried
customnext without any further purification

Sources & evidence

ORD record: ord-e19b36ca032b4e94a779c26bad071352
Source dataset: uspto-grants-2011_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07981890B2

Reaction notes

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