Water → HCID 9943313, compound

HRID 983394Notes

Reaction equation

HRID 983394 reaction equation
[Cl:1][C:2]1[C:7]([F:8])=[CH:6][N:5]=[C:4]([CH:9]([CH:13]2[CH2:15][CH2:14]2)[C:10]([NH2:12])=[O:11])[C:3]=1[CH3:16].Cl[C:18](Cl)([O:20]C(=O)OC(Cl)(Cl)Cl)Cl.CC(C)([O-])C.[K+].O>ClCCl>[Cl:1][C:2]1[C:7]([F:8])=[CH:6][N:5]2[C:18](=[O:20])[NH:12][C:10](=[O:11])[C:9]([CH:13]3[CH2:15][CH2:14]3)=[C:4]2[C:3]=1[CH3:16]

Participants

6

Reactant 4

HCID 962WaterHCID 94429TriphosgeneHCID 11172560HCID 11172560, compoundHCID 23665647Potassium tert-butoxide

Product 1

HCID 9943313HCID 9943313, compoundYield 67.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-50 °C

Procedure

To a −60° C. solution of 2-(4-chloro-5-fluoro-3-methylpyridin-2-yl)-2-cyclopropylacetamide (2.7 g, 11.0 mmol (Example 1)) and triphosgene (7.2 g, 24.0 mmol) in dichloromethane (250 mL) was added portionwise potassium tert-butoxide (4.5 g, 40.0 mmol). After the addition was complete, the mixture was stirred at −50° C. for 30 minutes. Water was then added at this temperature. The organic layer was separated, washed with brine (3×), dried over sodium sulfate, filtered, and evaporated. The residue was purified by column chromatography (7:3 ethyl acetate/hexanes) to afford the title compound (2 g). 1H NMR (200 MHz, CDCl3) δ 8.95 (bs, 1H), 8.16 (d, 1H), 2.66 (s, 3H), 1.75-1.71 (m, 1H), 1.11-1.01 (m, 2H), 0.46-0.37 (m, 2H). MSCI: m/z=269 (MH+).

Workup

  1. additionAfter the addition
  2. customThe organic layer was separated
  3. washwashed with brine (3×)
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. customevaporated
  7. customThe residue was purified by column chromatography (7:3 ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-c224f5f7d22e4230b4aa721a65452935
Source dataset
uspto-grants-2005_03
Patent number
US06864259B2

Reaction notes

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