Hydrochloric Acid → HCID 117965908, compound

HRID 2170933Notes

Reaction equation

HRID 2170933 reaction equation
N1CCOCC1.[Br:7][C:8]1[CH:16]=[CH:15][C:14]([F:17])=[C:13]2[C:9]=1[CH2:10][CH2:11][C@H:12]2[O:18][C:19]1[CH:31]=[CH:30][C:22]2[C@H:23]([CH2:26][C:27]([OH:29])=[O:28])[CH2:24][O:25][C:21]=2[CH:20]=1.Cl>CCO.O>[Br:7][C:8]1[CH:16]=[CH:15][C:14]([F:17])=[C:13]2[C:9]=1[CH2:10][CH2:11][C@H:12]2[O:18][C:19]1[CH:31]=[CH:30][C:22]2[C@H:23]([CH2:26][C:27]([OH:29])=[O:28])[CH2:24][O:25][C:21]=2[CH:20]=1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 117965907HCID 117965907, compound

Product 1

HCID 117965908HCID 117965908, compound

Reagents, catalysts & solvents 1

HCID 19096565Water ethanolSolvent

Procedure

30.0 g (60.7 mmol) [(S)-6-((R)-4-bromo-7-fluoroindan-1-yloxy)-2,3-dihydrobenzo-furan-3-yl]-acetic acid morpholine salt is dissolved in 480 ml EtOH/water (1:1) and 6.30 ml conc. HCl (64.0 mmol, 37%) is added. The mixture is heated to reflux and stirred for 30 min. After cooling in an ice bath the suspension is filtered off, washed with cold water and dried to yield [(S)-6-((R)-4-bromo-7-fluoroindan-1-yloxy)-2,3-dihydrobenzo-furan-3-yl]-acetic acid. b) Under argon, 30.0 g (73.7 mmol) [(S)-6-((R)-4-bromo-7-fluoroindan-1-yloxy)-2,3-dihydrobenzo-furan-3-yl]-acetic acid, 20.6 g (81.0 mmol) bis(pinacolato)diboron and 16.3 g (166 mmol) potassium acetate are suspended in 150 ml 2-methyltetrahydrofuran. The mixture is degassed and 165 mg (0.74 mmol) palladium(II) acetate and 528 mg (1.47 mmol) di(1-adamantyl)-n-butylphosphine are added. The mixture is degassed again and heated to 80° C. until completion of the reaction. Then, 150 ml water is added at 70° C. The aqueous phase is separated and the organic phase is cooled to r.t. and stirred overnight. The resulting suspension is cooled to 0° C. and 75 ml MCH is added. The crude product is filtered off, washed with cold 2-methyltetrahydrofuran/methylcyclohexane (2:1) and cold methylcyclohexane and dried. Further purification is achieved by recrystallization from 2-methyltetrahydrofuran or suspending the product in methylcyclohexane. Yield: 24.4 g; Rf=0.69 (PE/EtOAc/AcOH=0.69); Mass spectrum (ESI): m/z=455 [M+H]+.

Workup

  1. temperatureThe mixture is heated
  2. temperatureto reflux
  3. temperatureAfter cooling in an ice bath the suspension
  4. filtrationis filtered off
  5. washwashed with cold water
  6. customdried

Sources & evidence

ORD record
ord-ff177f90c5de4361a2a3bf6cd025ba88
Source dataset
uspto-grants-2015_06
Patent number
US09051289B2

Reaction notes

Loading…