2-Bromo-4-chloro-1-fluorobenzene → tert-Butyl 4-(5-chloro-2-fluorobenzoyl)piperidine-1-carboxylate

HRID 713177Notes

Reaction equation

HRID 713177 reaction equation
Br[C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[F:9].[Li]CCCC.CON(C)[C:18]([CH:20]1[CH2:25][CH2:24][N:23]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:22][CH2:21]1)=[O:19]>C1COCC1>[Cl:8][C:6]1[CH:5]=[CH:4][C:3]([F:9])=[C:2]([CH:7]=1)[C:18]([CH:20]1[CH2:25][CH2:24][N:23]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:22][CH2:21]1)=[O:19]

Participants

5

Reactant 3

HCID 27732642-Bromo-4-chloro-1-fluorobenzeneHCID 11065582tert-Butyl 4-(methoxy(methyl)carbamoyl)piperidine-1-carboxylateHCID 178418339Butyllithium

Product 1

HCID 49761188tert-Butyl 4-(5-chloro-2-fluorobenzoyl)piperidine-1-carboxylateYield 92%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 2-bromo-4-chloro-1-fluorobenzene (175 μL, 1.377 mmol) in THF (4.59 mL) at 78° C. was treated with n-BuLi (2.6 M, 741 μL, 1.928 mmol) and the reaction mixture was stirred for 30 min. To this was added tert-butyl 4-(methoxy(methyl)carbamoyl)piperidine-1-carboxylate (250 mg, 0.918 mmol) in one portion. The cooling bath was removed and the resulting reaction mixture was allowed to warm to rt and stirred for 1.5 h. Purification by automated flash silica gel chromatography using 10% EtOAc in hexanes afforded tert-butyl 4-(5-chloro-2-fluorobenzoyl)piperidine-1-carboxylate (287.9 mg, 92%) as a yellow oil. ESI-MS m/z [M+Na]+ 364.20.

Workup

  1. customThe cooling bath was removed
  2. customthe resulting reaction mixture
  3. stirringstirred for 1.5 h
  4. customPurification by automated flash silica gel chromatography

Sources & evidence

ORD record
ord-3a194604a7c247f898c8f91a4de55ef5
Source dataset
uspto-grants-2015_11
Patent number
US09181249B2

Reaction notes

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