1,2-Dibromoethane → HCID 71257370, compound

HRID 2200813Notes

Reaction equation

HRID 2200813 reaction equation
[O:1]1[C:5]2([CH2:10][CH2:9][CH:8]([O:11][C:12]3[N:17]=[C:16]([C:18]([F:21])([F:20])[F:19])[N:15]=[C:14]([CH2:22][C:23]([O:25][CH3:26])=[O:24])[CH:13]=3)[CH2:7][CH2:6]2)[O:4][CH2:3][CH2:2]1.Br[CH2:28][CH2:29]Br.[H-].[Na+]>O1CCCC1>[O:4]1[C:5]2([CH2:10][CH2:9][CH:8]([O:11][C:12]3[N:17]=[C:16]([C:18]([F:21])([F:19])[F:20])[N:15]=[C:14]([C:22]4([C:23]([O:25][CH3:26])=[O:24])[CH2:29][CH2:28]4)[CH:13]=3)[CH2:7][CH2:6]2)[O:1][CH2:2][CH2:3]1

Participants

5

Reactant 3

HCID 78391,2-DibromoethaneHCID 24758Sodium hydrideHCID 86676929HCID 86676929, compound

Product 1

HCID 71257370HCID 71257370, compoundYield 35.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

Methyl [6-(1,4-dioxaspiro[4.5]dec-8-yloxy)-2-(trifluoromethyl)pyrimidin-4-yl]acetate (0.46 g, 1.2 mmol) was dissolved in tetrahydrofuran (23 mL), then 1,2-dibromoethane (300 μL, 3.4 mmol) was added and the reaction mixture cooled to 0° C. NaH in mineral oil (136 mg, 3.4 mmol) was then added and the reaction mixture was heated to 67° C. for 18 h. LCMS showed 50% reaction. The reaction was quenched with saturated NH4Cl and was partitioned between EtOAc and water. The EtOAc extract was washed with brine, dried (Na2SO4), and stripped in vacuo. The ester was purified by automatic silica gel chromatography on a 40 g silica gel column, using solvent A=hexane; solvent B=EtOAc; flow 40 mL/min; A, 2 min; Gradient to 30% B in 30 min; detector set at 254 nm; collected 47 mL fractions; retention time starting ester, 26 min; product, 19 min. The solvent was removed by rotary evaporation to give 0.17 g of product. 1H NMR (300 MHz, CDCl3) δ 7.35 (s, 1H); 5.30 (m, 1H); 3.97 (s, 4H); 3.74 (s, 3H); 1.8-2.0 (m, 6H); 1.6-1.8 (m, 6H).

Workup

  1. temperaturethe reaction mixture was heated to 67° C. for 18 h
  2. custom50% reaction
  3. customThe reaction was quenched with saturated NH4Cl
  4. customwas partitioned between EtOAc and water
  5. extractionThe EtOAc extract
  6. washwas washed with brine
  7. dry with materialdried (Na2SO4)
  8. customThe ester was purified by automatic silica gel chromatography on a 40 g silica gel column
  9. custom2 min
  10. customcollected 47 mL fractions
  11. customester, 26 min
  12. customproduct, 19 min
  13. customThe solvent was removed by rotary evaporation

Sources & evidence

ORD record
ord-0e6eb90b4d444fbbb8659919cf34cd11
Source dataset
uspto-grants-2016_06
Patent number
US09359358B2

Reaction notes

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