Hydrochloric Acid → 3-Bromo-5-[ethyl(oxan-4-yl)amino]-2-fluoro-6-methylbenzoic acid

HRID 1616460Notes

Reaction equation

HRID 1616460 reaction equation
[Br:1][C:2]1[C:3]([F:22])=[C:4]([C:9]([CH3:21])=[C:10]([N:12]([CH2:19][CH3:20])[CH:13]2[CH2:18][CH2:17][O:16][CH2:15][CH2:14]2)[CH:11]=1)[C:5]([O:7]C)=[O:6].[OH-].[Na+].Cl>O1CCCC1.CO>[Br:1][C:2]1[C:3]([F:22])=[C:4]([C:9]([CH3:21])=[C:10]([N:12]([CH2:19][CH3:20])[CH:13]2[CH2:18][CH2:17][O:16][CH2:15][CH2:14]2)[CH:11]=1)[C:5]([OH:7])=[O:6]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 86672663Methyl 3-bromo-5-[ethyl(oxan-4-yl)amino]-2-fluoro-6-methylbenzoate

Product 1

HCID 866726643-Bromo-5-[ethyl(oxan-4-yl)amino]-2-fluoro-6-methylbenzoic acidYield 105.1%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of methyl 3-bromo-5-[ethyl(oxan-4-yl)amino]-2-fluoro-6-methylbenzoate (519 mg, 1.39 mmol) in Tetrahydrofuran (13 ml) and MeOH (4 ml) was added 4M NaOH (13.87 ml). The reaction mixture was stirred at 50° C. in air for 72 hours. The reaction mixture was acidified to pH 2-3 with 6M HCl and extracted with DCM (5×15 ml). The combined organic extracts were dried over MgSO4, filtered and concentrated under reduced pressure to give 526 mg (95%) of 3-bromo-5-[ethyl(oxan-4-yl)amino]-2-fluoro-6-methylbenzoic acid as a beige foam. LC-MS 88%, 1.77 min (3 minute LC-MS method), m/z=359.9/361.9, 1H NMR (500 MHz, Chloroform-d) δ ppm 7.43-7.31 (m, 1H), 4.00 (d, J=11.3 Hz, 2H), 3.41-3.29 (m, 2H), 3.16-2.91 (m, 3H), 2.40 (s, 3H), 1.84-1.59 (m, 4H), 0.99-0.82 (m, 3H).

Workup

  1. extractionextracted with DCM (5×15 ml)
  2. dry with materialThe combined organic extracts were dried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-e63a69196bdd448fbae9ffdff520cd2c
Source dataset
uspto-grants-2014_07
Patent number
US08765732B2

Reaction notes

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