Hexane → Tert-butyl 4-(6-bromopyridin-2-yl)-4-hydroxyazepane-1-carboxylate

HRID 57949Notes

Reaction equation

Br[C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Br:8])[N:3]=1.[Li]CCCC.CCCCCC.[O:20]=[C:21]1[CH2:27][CH2:26][CH2:25][N:24]([C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH2:23][CH2:22]1>CCOCC.O>[Br:8][C:4]1[N:3]=[C:2]([C:21]2([OH:20])[CH2:27][CH2:26][CH2:25][N:24]([C:28]([O:30][C:31]([CH3:33])([CH3:32])[CH3:34])=[O:29])[CH2:23][CH2:22]2)[CH:7]=[CH:6][CH:5]=1

Participants

Conditions

Temperature: -78 °C

Procedure

To a solution of 2,6-dibromopyridine (0.2 g, 0.84 mmol) in Et2O (20 mL) at −78° C. was added 2.5 M solution of n-BuLi in hexane (3.7 mL, 0.928 mmol) over 30 min. The mixture was stirred at −78° C. for 30 minutes. To it was dropped tert-butyl 4-oxoazepane-1-carboxylate (180 mg, 084 mmol) in Et2O (20 mL) over 15 minutes. After the mixture was stirred for one hour, to it was added H2O (100 mL). The aqueous layer was extracted with EtOAc (100 mL×2). The combined organic layers were washed with 10% solution of NaOH and brine, dried over MgSO4, concentrated under reduced pressure. The crude product was purified by silica gel chromatography using petroleum ether/EtOAc (9:1) as eluting solvents to afford tert-butyl 4-(6-bromopyridin-2-yl)-4-hydroxyazepane-1-carboxylate as an oil (200 mg, 62.5%). MS (ESI) m/z: 371 [M+H]+.

Workup

stirringAfter the mixture was stirred for one hour, to it
extractionThe aqueous layer was extracted with EtOAc (100 mL×2)
washThe combined organic layers were washed with 10% solution of NaOH and brine
dry with materialdried over MgSO4
concentrationconcentrated under reduced pressure
customThe crude product was purified by silica gel chromatography
washas eluting solvents

Sources & evidence

ORD record: ord-cde0a8fc69934474b8a901d6cd13b4aa
Source dataset: uspto-grants-2016_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09434725B2

Reaction notes

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