Hydrochloric Acid → 8-bromo-2-((tert-butoxycarbonyl)amino)-3H-benzo[b]azepine-4-carboxylic acid

HRID 593441

Reaction equation

HRID 593441 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]2=[C:6]([CH:25]=1)[N:7]=[C:8]([NH:17][C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:9][C:10]([C:12]([O:14]CC)=[O:13])=[CH:11]2.[OH-].[Na+].Cl>C1COCC1>[Br:1][C:2]1[CH:3]=[CH:4][C:5]2=[C:6]([CH:25]=1)[N:7]=[C:8]([NH:17][C:18]([O:20][C:21]([CH3:23])([CH3:22])[CH3:24])=[O:19])[CH2:9][C:10]([C:12]([OH:14])=[O:13])=[CH:11]2

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 58228529Ethyl 8-bromo-2-((tert-butoxycarbonyl)amino)-3H-benzo[b]azepine-4-carboxylate

Product 1

HCID 669596238-bromo-2-((tert-butoxycarbonyl)amino)-3H-benzo[b]azepine-4-carboxylic acidYield 54%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (1E,4E)-ethyl 8-bromo-2-(tert-butoxycarbonylamino)-3H-benzo[b]azepine-4-carboxylate (15.0 g, 36.7 mmol) in THF (195 mL) at −15° C. was slowly added 1N aq NaOH (55.0 ml, 55.0 mmol) over 10 min. The reaction mixture was warmed to room temperature and stirred for 18 h. The reaction mixture was poured into ice-cold water (500 mL). The pH of the mixture was carefully adjusted to 5-6 with 0.5 N aq HCl (˜260 mL). The resulting mixture was extracted with EtOAc. The aqueous layer was extracted with EtOAc (1×). The combined organic layers were washed with brine, dried over MgSO4, filtered while rinsing with EtOAc, and concentrated under reduced pressure to give the crude material that was triturated with MeCN (20 mL). The solids were filtered off and dried under reduced pressure to afford 7.56 g (54%) of the desired product. The filtrate was concentrated under reduced pressure again to give the second crude material that was triturated with MeCN again to afford additional 1.33 g (9.5%) of the product. Total 8.89 g (64%) of (1E,4E)-8-bromo-2-(tert-butoxycarbonylamino)-3H-benzo[b]azepine-4-carboxylic acid was obtained. MS APCI(+) m/z 381, 383 (M+1, Br pattern) detected.

Workup

  1. customat −15° C.
  2. customover 10 min
  3. extractionThe resulting mixture was extracted with EtOAc
  4. extractionThe aqueous layer was extracted with EtOAc (1×)
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. washwhile rinsing with EtOAc
  9. concentrationconcentrated under reduced pressure
  10. customto give the crude material that
  11. customwas triturated with MeCN (20 mL)
  12. filtrationThe solids were filtered off
  13. customdried under reduced pressure

Sources & evidence

ORD record
ord-0e946798dfdf43ddb0b87e2eb05bbe48
Source dataset
uspto-grants-2016_01
Patent number
US09242964B2

Linked notes

Loading…