Methanol → 3-((3-Bromo-2-methylphenylamino)methyl)-5-tert-butylthiophene-2-carboxylic Acid

HRID 1772076Notes

Reaction equation

HRID 1772076 reaction equation
[Br:1][C:2]1[C:3]([CH3:23])=[C:4]([NH:8][CH2:9][C:10]2[CH:14]=[C:13]([C:15]([CH3:18])([CH3:17])[CH3:16])[S:12][C:11]=2[C:19]([O:21]C)=[O:20])[CH:5]=[CH:6][CH:7]=1.C1COCC1.CO.[OH-].[Li+]>O>[Br:1][C:2]1[C:3]([CH3:23])=[C:4]([NH:8][CH2:9][C:10]2[CH:14]=[C:13]([C:15]([CH3:17])([CH3:18])[CH3:16])[S:12][C:11]=2[C:19]([OH:21])=[O:20])[CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 887MethanolHCID 3939Lithium HydroxideHCID 8028TetrahydrofuranHCID 86697931Methyl 3-((3-Bromo-2-methylphenylamino)methyl)-5-tert-butylthiophene-2-carboxylate

Product 1

HCID 866979323-((3-Bromo-2-methylphenylamino)methyl)-5-tert-butylthiophene-2-carboxylic AcidYield 99.7%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A 50-mL single-necked round-bottomed flask equipped with a magnetic stirrer was charged with 102d (1.30 g, 3.28 mmol), THF (5.0 mL), methanol (5.0 mL) and water (5.0 mL). Lithium hydroxide (1.38 g, 32.8 mmol) was added and the mixture was placed in a 40° C. oil bath. After 16 h the reaction mixture was cooled to room temperature and the volatiles removed under reduced pressure. The resulting aqueous solution was acidified with 2 N hydrochloric acid to pH of 4. The resulting solid was filtered off and dried in a vacuum oven at 40° C. affording a quantitative yield (1.25 g) of 102e as a white solid: mp 150-152° C.; 1H NMR (300 MHz, DMSO-d6) δ 6.85 (t, 1H, J=7.8 Hz), 6.75-6.67 (m, 3H), 4.35 (s, 2H), 2.18 (s, 3H), 1.26 (s, 9H); MS (APCI−) m/z 380.2 (M−H).

Workup

  1. customA 50-mL single-necked round-bottomed flask equipped with a magnetic stirrer
  2. customwas placed in a 40° C.
  3. customthe volatiles removed under reduced pressure
  4. filtrationThe resulting solid was filtered off
  5. customdried in a vacuum oven at 40° C.

Sources & evidence

ORD record
ord-4c5522d7aa9144fd8012b2ec1b0e2121
Source dataset
uspto-grants-2016_02
Patent number
US09249123B2

Reaction notes

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