2,6-Dibromopyridine → tert-Butyl 4-(6-bromopyridin-2-yl)-4-hydroxypiperidine-1-carboxylate

HRID 2039720Notes

Reaction equation

HRID 2039720 reaction equation
Br[C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Br:8])[N:3]=1.C([Li])CCC.[C:14]([O:18][C:19]([N:21]1[CH2:26][CH2:25][C:24](=[O:27])[CH2:23][CH2:22]1)=[O:20])([CH3:17])([CH3:16])[CH3:15].[Cl-].[NH4+]>ClCCl>[C:14]([O:18][C:19]([N:21]1[CH2:26][CH2:25][C:24]([OH:27])([C:2]2[CH:7]=[CH:6][CH:5]=[C:4]([Br:8])[N:3]=2)[CH2:23][CH2:22]1)=[O:20])([CH3:17])([CH3:15])[CH3:16]

Participants

6

Reactant 4

HCID 122742,6-DibromopyridineHCID 25517Ammonium ChlorideHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylate2×HCID 178418339Butyllithium

Product 1

HCID 86614831tert-Butyl 4-(6-bromopyridin-2-yl)-4-hydroxypiperidine-1-carboxylateYield 98.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

As shown in FIG. 7—step i, to a solution of 2,6-dibromopyridine (4.738 g) in dichloromethane (80 mL) was added dropwise n-butyllithium (2.5 N, 8.9 mL) at or below −65° C., followed by stirring at this temperature for 20 min. 4-Oxo-piperidine-1-carboxylic acid tert-butyl ester (compound 1030) (4.38 g) was added. After 15 min, the temperature was brought up to −30° C. and a saturated aqueous ammonium chloride solution (100 mL) was added. The organic and aqueous layers were separated, the aqueous layer extracted with dichloromethane (2×80 mL). The combined organics were evaporated to gave a residue which was triturated with hexane to give 6-bromo-4′-hydroxy-3′,4′,5′,6′-tetrahydro-2′H-[2,4′]bipyridinyl-1′-carboxylic acid tert-butyl ester (compound 1031) as a white solid (7.05 g).

Workup

  1. waitAfter 15 min
  2. customwas brought up to −30° C.
  3. customThe organic and aqueous layers were separated
  4. extractionthe aqueous layer extracted with dichloromethane (2×80 mL)
  5. customThe combined organics were evaporated
  6. customto gave a residue which
  7. customwas triturated with hexane

Sources & evidence

ORD record
ord-d91c675f6c1e4ac18b5423fedf646004
Source dataset
uspto-grants-2013_11
Patent number
US08580802B2

Reaction notes

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