Methanol → 5-((1R)-2-bromo-1-hydroxyethyl)-8-phenylmethoxy-1H-quinolin-2-one

HRID 407124Notes

Reaction equation

[CH2:1]([O:8][C:9]1[CH:10]=[CH:11][C:12]([C:20](=[O:23])[CH2:21][Br:22])=[C:13]2[C:18]=1[NH:17][C:16](=[O:19])[CH:15]=[CH:14]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.O1CCCC1.B.CO>C1(C)C=CC=CC=1>[CH2:1]([O:8][C:9]1[CH:10]=[CH:11][C:12]([C@@H:20]([OH:23])[CH2:21][Br:22])=[C:13]2[C:18]=1[NH:17][C:16](=[O:19])[CH:15]=[CH:14]2)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

Conditions

Temperature: -10 °C

Procedure

8-Benzyloxy 5-(2-bromoacetyl)-1H-quinolin-2-one (90.0 g, 243 mmol) was placed under nitrogen and tetrahydrofuran (900 mL) was added followed by the catalyst described above (1.8 M in toluene, 15 mL, 27 mmol). The suspension was cooled to −10±5° C. in an ice/isopropanol bath. Borane (1.0 M in THF, 294 mL, 294 mmol) was added over 4 h. The reaction was then stirred an additional 45 min at −10° C. and then methanol (250 mL) was added slowly. The mixture was concentrated under vacuum and the residue was dissolved in boiling acetonitrile (1.3 L), filtered while hot and then cooled to room temperature. The crystals were filtered, washed with acetonitrile and dried under vacuum to give the title compound (72.5 g, 196 mmol, 81% yield, 95% ee, 95% pure by HPLC).

Workup

concentrationThe mixture was concentrated under vacuum
dissolutionthe residue was dissolved
filtrationfiltered while hot and
temperaturethen cooled to room temperature
filtrationThe crystals were filtered
washwashed with acetonitrile
customdried under vacuum

Sources & evidence

ORD record: ord-e49b1d61d0a042359455c264e16f661c
Source dataset: uspto-grants-2014_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08754223B2

Reaction notes

Loading…