Ammonium Chloride → HCID 178501089, compound

HRID 2283489Notes

Reaction equation

HRID 2283489 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5](I)=[N:6][CH:7]=1.C([Mg]Cl)(C)C.[Li+].[Cl-].[C:16]([C@H:19]1[CH2:24][CH2:23][C@H:22]([C:25]([O:27][CH3:28])=[O:26])[CH2:21][CH2:20]1)(=[O:18])[CH3:17].[BH4-].[Na+].[NH4+].[Cl-]>C1COCC1.C(Cl)Cl>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([C:16]([C@H:19]2[CH2:24][CH2:23][C@H:22]([C:25]([O:27][CH3:28])=[O:26])[CH2:21][CH2:20]2)([OH:18])[CH3:17])=[N:6][CH:7]=1

Participants

8

Reactant 5

HCID 25517Ammonium ChlorideHCID 5936905-Bromo-2-iodopyridineHCID 4311764Sodium borohydrideHCID 178461733HCID 178461733, compoundHCID 178501092HCID 178501092, compound

Product 1

HCID 178501089HCID 178501089, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 5-bromo-2-iodopyridine (18.5 g, 65.1 mmol) in THF (33 mL) at −5° C. was slowly added a solution of i-PrMgCl—LiCl (1.3 M in THF, 50.1 mL, 65.1 mmol) at such a rate that the internal temperature did not exceed −2° C. The reaction mixture was allowed to stir for 1.25 hours at 0° C., and methyl trans-4-acetylcyclohexanecarboxylate (6 g, 32.6 mmol) was added dropwise via syringe. The reaction mixture was stirred for an additional 1 hour at 0° C., then sodium borohydride (0.62 g, 16.3 mmol) was added. The reaction mixture was slowly allowed to warm to room temperature and stirred for 14 hours. The mixture was diluted by addition of saturated aqueous NH4Cl (200 mL) and DCM (250 mL). The layers were separated and the aqueous layer extracted with DCM (250 mL). The combined organic layers were dried with MgSO4, filtered, and concentrated in vacuo. The crude residue was absorbed on silica, gel and purified via silica gel column chromatography (EtOAc/Hexanes) to afford racemic methyl trans-4-[1-(5-bromopyridin-2-yl)-1-hydroxyethyl]cyclohexane carboxylate as a yellow oil. MS ESI calcd. for C15H21BrNO3 [M+H]+ 342 and 344. found 342 and 344. 1H NMR (600 MHz, CDCl3) δ 8.54 (d, J=1.8 Hz, 1H), 7.79 (dd, J=8.4, 2.3 Hz, 1H), 7.19 (d, J=8.4 Hz, 1H), 4.65 (s, 1H), 3.61 (s, 3H), 2.16 (m, 1H), 2.05-1.97 (m, 1H), 1.97-1.90 (m, 1H), 1.90-1.83 (m, 1H), 1.56 (m, 1H), 1.45 (s, 3H), 1.37 (m, 1H), 1.31-1.15 (m, 3H), 1.09 (m, 1H).

Workup

  1. customdid not exceed −2° C
  2. stirringThe reaction mixture was stirred for an additional 1 hour at 0° C.
  3. temperatureto warm to room temperature
  4. stirringstirred for 14 hours
  5. customThe layers were separated
  6. extractionthe aqueous layer extracted with DCM (250 mL)
  7. dry with materialThe combined organic layers were dried with MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe crude residue was absorbed on silica, gel
  11. custompurified via silica gel column chromatography (EtOAc/Hexanes)

Sources & evidence

ORD record
ord-7a806b77ceaf41c98c723c7184869116
Source dataset
uspto-grants-2015_09
Patent number
US09145391B2

Reaction notes

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