Boron trifluoride etherate → (2R)-1-{4-[({(1R,2R)-2-[1-(5-ethylpyrimidin-2-yl)piperidin-4-yl]cyclopropyl}methoxy)methyl]phenyl}propan-2-ol

HRID 1468843Notes

Reaction equation

HRID 1468843 reaction equation
Br[C:2]1[CH:27]=[CH:26][C:5]([CH2:6][O:7][CH2:8][C@@H:9]2[CH2:11][C@@H:10]2[CH:12]2[CH2:17][CH2:16][N:15]([C:18]3[N:23]=[CH:22][C:21]([CH2:24][CH3:25])=[CH:20][N:19]=3)[CH2:14][CH2:13]2)=[CH:4][CH:3]=1.C([Li])CCC.[CH2:33]1[O:36][C@@H:34]1[CH3:35].B(F)(F)F.CCOCC>C1COCC1.CCCCCC>[CH2:24]([C:21]1[CH:20]=[N:19][C:18]([N:15]2[CH2:16][CH2:17][CH:12]([C@H:10]3[CH2:11][C@H:9]3[CH2:8][O:7][CH2:6][C:5]3[CH:26]=[CH:27][C:2]([CH2:33][C@H:34]([OH:36])[CH3:35])=[CH:3][CH:4]=3)[CH2:13][CH2:14]2)=[N:23][CH:22]=1)[CH3:25]

Participants

7

Reactant 4

HCID 8000Boron trifluoride etherateHCID 146261(R)-1,2-EpoxypropaneHCID 711352722-[4-((1R,2R)-2-{[(4-bromobenzyl)oxy]methyl}cyclopropyl)piperidin-1-yl]-5-ethyl pyrimidineHCID 178418339Butyllithium

Product 1

HCID 71135273(2R)-1-{4-[({(1R,2R)-2-[1-(5-ethylpyrimidin-2-yl)piperidin-4-yl]cyclopropyl}methoxy)methyl]phenyl}propan-2-ol

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8058HexaneSolvent

Conditions

Temperature
-78 °C

Procedure

The product of example 54 (step A) (100 mg, 0.2 mmol), was dissolved in THF (2.3 mL), and the solution was cooled to −78° C. under N2. n-Butyl lithium (0.1 mL of a 2.5 M solution in hexane, 0.25 mmol) was added dropwise at 78° C. The solution was stirred at −78° C. for 20 minutes. (R)-propylene oxide (16 mg, 0.028 mmol) and BF3.Et2O (33 mg, 0.23 mmol) were then added. The solution was stirred at −78° C. for 30 minutes, and then at RT for 1 h. The solution was partitioned between water and DCM. The aqueous layer was extracted with DCM. The combined organic layers were dried (Na2SO4), filtered, and concentrated in vacuo. The residue was purified via silica gel column chromatography (2/1 hexanes/EtOAc) to provide the title compound. MS (ESI) m/z 410 [M+H]+. GPR119 Human EC50: 11 nM

Workup

  1. stirringThe solution was stirred at −78° C. for 30 minutes
  2. waitat RT for 1 h
  3. customThe solution was partitioned between water and DCM
  4. extractionThe aqueous layer was extracted with DCM
  5. dry with materialThe combined organic layers were dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified via silica gel column chromatography (2/1 hexanes/EtOAc)

Sources & evidence

ORD record
ord-1d878f2d3cf54c31b43923b91957f82d
Source dataset
uspto-grants-2015_04
Patent number
US09006228B2

Reaction notes

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