Dimethylformamide → 8-[3-Fluoro-5-(trifluoromethyl)pyridin-2-yl]-1,4-dioxa-8-azaspiro[4.5]decane

HRID 1409741Notes

Reaction equation

HRID 1409741 reaction equation
[O:1]1[C:5]2([CH2:10][CH2:9][NH:8][CH2:7][CH2:6]2)[O:4][CH2:3][CH2:2]1.Br[C:12]1[C:17]([F:18])=[CH:16][C:15]([C:19]([F:22])([F:21])[F:20])=[CH:14][N:13]=1.CN(C)C=O.O1CCOCC1>C(N(CC)CC)C>[F:18][C:17]1[C:12]([N:8]2[CH2:9][CH2:10][C:5]3([O:4][CH2:3][CH2:2][O:1]3)[CH2:6][CH2:7]2)=[N:13][CH:14]=[C:15]([C:19]([F:21])([F:20])[F:22])[CH:16]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 312751,4-DioxaneHCID 674351,4-Dioxa-8-azaspiro(4.5)decaneHCID 155928232-Bromo-3-fluoro-5-(trifluoromethyl)pyridine

Product 1

HCID 682902228-[3-Fluoro-5-(trifluoromethyl)pyridin-2-yl]-1,4-dioxa-8-azaspiro[4.5]decane

Reagents, catalysts & solvents 1

HCID 8471TriethylamineSolvent

Procedure

1,4-Dioxa-8-azaspiro[4.5]decane (1.76 g), 2-bromo-3-fluoro-5-(trifluoromethyl)-pyridine (2.95 g), N,N-dimethylformamide (50 mL), 1,4-dioxane (75 mL) and triethylamine (5.07 ml) are heated in a sealed vessel at 120° C. with stirring for 1 h. After cooling the mixture is concentrated and partitioned between ethyl acetate (100 mL) and water (100 mL). The water layer is extracted with ethyl acetate (100 mL) and the combined ethyl acetate layers are dried over Na2SO4, filtered and concentrated to give the title compound. LC (method 21): tR=7.59 min; Mass spectrum (APCI): m/z=307 [M+H]+.

Workup

  1. temperatureAfter cooling the mixture
  2. concentrationis concentrated
  3. custompartitioned between ethyl acetate (100 mL) and water (100 mL)
  4. extractionThe water layer is extracted with ethyl acetate (100 mL)
  5. dry with materialthe combined ethyl acetate layers are dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-260e1efef6864c2a9618626ea995e425
Source dataset
uspto-grants-2014_12
Patent number
US08921398B2

Reaction notes

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