2-Bromo-5-chloropyridine → HCID 178451146, compound

HRID 2283488Notes

Reaction equation

HRID 2283488 reaction equation
C([Li])(C)(C)C.Br[C:7]1[CH:12]=[CH:11][C:10]([Cl:13])=[CH:9][N:8]=1.[C:14]([C@H:17]1[CH2:22][CH2:21][C@H:20]([C:23]([O:25][CH2:26][CH2:27][CH2:28][CH3:29])=[O:24])[CH2:19][CH2:18]1)(=[O:16])[CH3:15]>ClCCl.[Cl-].[NH4+]>[Cl:13][C:10]1[CH:11]=[CH:12][C:7]([C:14]([C@H:17]2[CH2:22][CH2:21][C@H:20]([C:23]([O:25][CH2:26][CH2:27][CH2:28][CH3:29])=[O:24])[CH2:19][CH2:18]2)([OH:16])[CH3:15])=[N:8][CH:9]=1

Participants

6

Reactant 3

HCID 8170982-Bromo-5-chloropyridineHCID 178418306HCID 178418306, compoundHCID 178451155HCID 178451155, compound

Product 1

HCID 178451146HCID 178451146, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 25517Ammonium ChlorideSolvent

Conditions

Temperature
-78 °C

Procedure

Tert-butyllithium (1.6 M in hexane, 3.3 mL, 5.28 mmol) was added dropwise over a period of 1 minute to a solution of 2-bromo-5-chloropyridine (0.8 g, 4.16 mmol) in dichloromethane (21 mL) at −78° C. The mixture was stirred for 90 minutes at −78° C., then a solution of trans-butyl 4-acetylcyclohexanecarboxylate (1.035 g, 4.57 mmol) in dichloromethane (1 mL) was added. The reaction was then allowed to warm to 23° C. over a period of 16 hours and subsequently diluted with saturated aqueous ammonium chloride solution. The resulting slurry was extracted with dichloromethane (3×70 mL), and the combined organic fractions were dried over sodium sulfate, filtered, and concentrated in vacuo. Purification of the residue by silica gel column chromatography (EtOAc/hexanes) afforded racemic trans-butyl 4-(1-(5-chloropyridin-2-yl)-1-hydroxyethyl)cyclohexanecarboxylate as a brown oil. MS ESI calcd. for C18H27ClNO3 [M+H]+ 340. found 340. 1H NMR (500 MHz, CDCl3) δ 8.47 (s, 1H), 7.68 (d, J=8.4 Hz, 1H), 7.26 (d, J=8.4 Hz, 1H), 4.68 (s, 1H), 4.03 (t, J=6.6 Hz, 2H), 2.22-1.85 (m, 4H), 1.66-1.53 (m, 4H), 1.48 (s, 3H), 1.42-1.05 (m, 6H), 0.91 (t, J=7.5 Hz, 3H).

Workup

  1. temperatureto warm to 23° C. over a period of 16 hours
  2. extractionThe resulting slurry was extracted with dichloromethane (3×70 mL)
  3. dry with materialthe combined organic fractions were dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customPurification of the residue by silica gel column chromatography (EtOAc/hexanes)

Sources & evidence

ORD record
ord-5a6f1a36334c4561b8469ff6c8b43ba4
Source dataset
uspto-grants-2015_09
Patent number
US09145391B2

Reaction notes

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