Hydrochloric Acid → HCID 22050576, compound

HRID 1867182Notes

Reaction equation

HRID 1867182 reaction equation
[Br:1][C:2]1[C:3](=[O:28])[N:4]([C:19]2[O:23][C:22]([C:24]([O:26]C)=[O:25])=[CH:21][CH:20]=2)[C:5]([CH3:18])=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][C:13]([F:16])=[CH:12][C:11]=1[F:17].[OH-].[Na+].Cl.C(#N)C.O>C1COCC1.C(OCC)(=O)C>[Br:1][C:2]1[C:3](=[O:28])[N:4]([C:19]2[O:23][C:22]([C:24]([OH:26])=[O:25])=[CH:21][CH:20]=2)[C:5]([CH3:18])=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][C:13]([F:16])=[CH:12][C:11]=1[F:17]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 18373917Acetonitrile--water (1/1)HCID 22049896HCID 22049896, compound

Product 1

HCID 22050576HCID 22050576, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

To a room temperature solution of methyl 5-[3-bromo-4-[(2,4-difluorobenzyl)oxy]-6-methyl-2-oxopyridin-1(2H)-yl]-2-furoate (step 2) (3.00 g, 6.61 mmol) in THF (20 mL) was added dropwise an aqueous solution of sodium hydroxide (3.0 M, 4.00 mL, 12.0 mmol). The reaction was then heated to 60° C. for 12.0 hours. The resulting suspension was then diluted with 800 mL of ethyl acetate and neutralized with an aqueous solution of hydrochloric acid (3.0 N, 4.0 mL, 12 mmol). The resulting biphasic solution was then concentrated in vacuo to a volume of 90 mL. At this time a white solid began to form and the resulting solid suspension was allowed to sit until precipitation appeared to stop (approximately 1.0 hour). The precipitate was collected and dried in vacuo (1.0 mm Hg) to furnish the solid acid as an intermediate (2.27 g, 78%). 1H NMR (400 MHz, d7-DMF) δ 7.79 (app q, J=8.0 Hz, 1H), 7.32 (t, J=9.2 Hz, 1H), 7.20 (app t, J=7.4 Hz, 1H), 6.88 (app d, J=2.5 Hz, 1H), 6.74 (s, 1H), 6.51 (d, J=2.5 Hz, 1H), 5.44 (s, 2H), 2.10 (s, 3H); LC/MS C-18 column, tr=2.77 minutes (5 to 95% acetonitrile/water over 5 minutes at 1 ml/min with detection 254 nm, at 50° C.). ES-MS m/z 440 (M+H). ES-HRMS m/z 439.9959 (M+H calcd for C18H13BrF2NO5 requires 439.9940).

Workup

  1. concentrationThe resulting biphasic solution was then concentrated in vacuo to a volume of 90 mL
  2. customto form
  3. customto sit until precipitation
  4. custom(approximately 1.0 hour)
  5. customThe precipitate was collected
  6. customdried in vacuo (1.0 mm Hg)
  7. customto furnish the solid acid as an intermediate (2.27 g, 78%)

Sources & evidence

ORD record
ord-a84aa32bf8bc4988ba7f8f22f5c9993b
Source dataset
uspto-grants-2009_12
Patent number
US07629363B2

Reaction notes

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