Dimethylformamide → HCID 86719972, compound

HRID 1617332Notes

Reaction equation

HRID 1617332 reaction equation
C(=O)([O-])[O-].[Cs+].[Cs+].[F:7][C:8]1[CH:13]=[CH:12][C:11]([OH:14])=[CH:10][N:9]=1.CN(C)C=O.Br[CH2:21][CH2:22][O:23][CH:24]1[CH2:29][CH2:28][CH2:27][CH2:26][O:25]1>CCOC(C)=O>[F:7][C:8]1[CH:13]=[CH:12][C:11]([O:14][CH2:21][CH2:22][O:23][CH:24]2[CH2:29][CH2:28][CH2:27][CH2:26][O:25]2)=[CH:10][N:9]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 10796Cesium carbonateHCID 866212-(2-Bromoethoxy)tetrahydro-2H-pyranHCID 27631086-Fluoropyridin-3-ol

Product 1

HCID 86719972HCID 86719972, compoundYield 91%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

Add cesium carbonate (3 Eq, 53.05 mmoles; 17.2 g) to a solution of 2-fluoro-5-hydroxypyridine (2.0 g, 1.00 Eq, 17.68 mmoles) in dimethylformamide (0.3 M; 762.37 mmoles; 59.0 mL), followed by 2-(2-bromoethoxy)tetrahydro-2H-pyran (17.7 mmoles, 3.7 g) and stir at room temperature overnight. Transfer to a separatory funnel and add EtOAc (500 mL). Wash organic layer, wash with water (300 mL) followed by brine (200 mL). Dry over Na2SO4, filter and concentrate. Purify the crude mixture by HPLC eluting with hexanes/EtOAc 7/3 to give 2-fluoro-5-[2-(tetrahydro-2H-pyran-2-yloxy)ethoxy]pyridine as a pale yellow oil (3.9 g, 16.2 mmoles; 91% yield). LCMS (Low) rt=1.8 min., M+1=242.

Workup

  1. washWash organic layer, wash with water (300 mL)
  2. dry with materialDry over Na2SO4
  3. filtrationfilter
  4. concentrationconcentrate
  5. customPurify the crude mixture by HPLC
  6. washeluting with hexanes/EtOAc 7/3

Sources & evidence

ORD record
ord-1cc7636aeb484faf8f5502714b756c9a
Source dataset
uspto-grants-2014_07
Patent number
US08765960B2

Reaction notes

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