Sodium hydride → HCID 71116042, compound

HRID 1468872Notes

Reaction equation

HRID 1468872 reaction equation
[H-].[Na+].[CH:3]([C:6]1[N:10]=[C:9]([N:11]2[CH2:16][CH2:15][CH:14]([C@H:17]3[CH2:19][C@H:18]3[CH2:20][OH:21])[CH2:13][CH2:12]2)[O:8][N:7]=1)([CH3:5])[CH3:4].[Br:22][C:23]1[CH:28]=[CH:27][C:26]([CH2:29]Br)=[C:25]([F:31])[CH:24]=1>CN(C=O)C>[Br:22][C:23]1[CH:28]=[CH:27][C:26]([CH2:29][O:21][CH2:20][C@@H:18]2[CH2:19][C@@H:17]2[CH:14]2[CH2:15][CH2:16][N:11]([C:9]3[O:8][N:7]=[C:6]([CH:3]([CH3:5])[CH3:4])[N:10]=3)[CH2:12][CH2:13]2)=[C:25]([F:31])[CH:24]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 27336604-Bromo-2-fluorobenzyl bromideHCID 71135284HCID 71135284, compound

Product 1

HCID 71116042HCID 71116042, compoundYield 89%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

Sodium hydride (203 mg, 5.09 mmol) was added to a stirring solution of ((1R,2R)-2-(1-(3-isopropyl-1,2,4-oxadiazol-5-yl)piperidin-4-yl)cyclopropyl)methanol (Step A product, 900 mg, 3.39 mmol) in DMF (9 mL) that had been cooled to 0° C. in an ice bath and placed under an inert atmosphere. 10 min later 4-bromo-1-(bromomethyl)-2-fluorobenzene (1 g, 3.73 mmol) was introduced to the mixture. The ice bath was removed and the reaction warmed to rt. The reaction was aged for 1 hr then diluted with EtOAc (20 mL) and neutralized by the slow addition of saturated aqueous ammonium chloride solution (20 mL). The layers were cut and the aqueous phase extracted with EtOAc (20 mL×2). The combined organic layers were dried over MgSO4, filtered, and concentrated under reduced pressure. The residue was loaded onto a silica column (KP-Sil 50 g SNAP column, Biotage system) eluting with a range of 0-45% EtOAc/Hex over 12 CV to give the desired compound (1.36 g, 89%). LC/MS (m/z): 452 (M+H)+.

Workup

  1. customThe ice bath was removed
  2. temperaturethe reaction warmed to rt
  3. additionthen diluted with EtOAc (20 mL)
  4. additionneutralized by the slow addition of saturated aqueous ammonium chloride solution (20 mL)
  5. extractionthe aqueous phase extracted with EtOAc (20 mL×2)
  6. dry with materialThe combined organic layers were dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. washeluting with a range of 0-45% EtOAc/Hex over 12 CV

Sources & evidence

ORD record
ord-6c48bc4cf91f40b1834b0f4227fbc748
Source dataset
uspto-grants-2015_04
Patent number
US09006228B2

Reaction notes

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