Dimethylamine → HCID 66549043, compound

HRID 2174375Notes

Reaction equation

HRID 2174375 reaction equation
[F:1][C:2]1([C:9]2[CH:14]=[CH:13][C:12]([C:15]3[CH2:19][C:18]([C:24]4[CH:29]=[C:28]([Cl:30])[C:27]([Cl:31])=[C:26]([Cl:32])[CH:25]=4)([C:20]([F:23])([F:22])[F:21])[O:17][N:16]=3)=[CH:11][CH:10]=2)[CH2:5][CH:4]([C:6]([OH:8])=O)[CH2:3]1.C(Cl)(=O)C(Cl)=O.[CH3:39][NH:40][CH3:41]>C(Cl)Cl>[CH3:39][N:40]([CH3:41])[C:6]([CH:4]1[CH2:5][C:2]([F:1])([C:9]2[CH:10]=[CH:11][C:12]([C:15]3[CH2:19][C:18]([C:24]4[CH:25]=[C:26]([Cl:32])[C:27]([Cl:31])=[C:28]([Cl:30])[CH:29]=4)([C:20]([F:23])([F:22])[F:21])[O:17][N:16]=3)=[CH:13][CH:14]=2)[CH2:3]1)=[O:8]

Participants

5

Reactant 3

HCID 674DimethylamineHCID 65578Oxalyl chlorideHCID 86707793HCID 86707793, compound

Product 1

HCID 66549043HCID 66549043, compoundYield 33%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of 3-Fluoro-3-{4-[5-(3,4,5-trichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-phenyl}-cyclobutanecarboxylic acid (Preparation 6, 0.1 g, 0.196 mmol) in DCM (2 mL) was added oxalyl chloride (0.023 g, 0.193 mmol) at 0° C. Reaction mixture was stirred at room temperature for 1 hour and cooled to 0° C. followed by addition of dimethyl amine (gas) was purged for 2 hours. Resulting reaction mixture was stirred at room temperature for 18 hours. After complete consumption of starting material, reaction mixture was diluted with DCM (3 mL), washed with water (3×3 mL). Organic layer was dried over sodium sulphate and evaporated in vacuo to get crude thick oil (0.077 g). Crude was purified by column chromatography on silica gel (100-200 mesh size), compound was eluted using 2% methanol in DCM and crystallized with chloroform:pentane (1:9) to afford off white solid (0.035 g, 33%). 1H-NMR (400 MHz, CDCl3) δ: 2.79-2.80 (m, 1H), 2.80-2.94 (m, 4H), 2.97 (s, 3H), 2.99 (s, 3H), 3.66-3.69 (m, 1H), 4.07 (d, 1H, J=17.16 Hz), 7.51 (d, 2H, J=8.16 Hz), 7.63-7.65 (m, 4H); LC-MS (m/z): [M−H] 535.0.

Workup

  1. customReaction mixture
  2. temperaturecooled to 0° C.
  3. customwas purged for 2 hours
  4. customResulting
  5. customreaction mixture
  6. stirringwas stirred at room temperature for 18 hours
  7. customAfter complete consumption of starting material, reaction mixture
  8. additionwas diluted with DCM (3 mL)
  9. washwashed with water (3×3 mL)
  10. dry with materialOrganic layer was dried over sodium sulphate
  11. customevaporated in vacuo
  12. customto get crude thick oil (0.077 g)
  13. customCrude was purified by column chromatography on silica gel (100-200 mesh size), compound
  14. washwas eluted
  15. customcrystallized with chloroform:pentane (1:9)

Sources & evidence

ORD record
ord-26f126ffc8584fa9b1ca307d37507cc0
Source dataset
uspto-grants-2015_06
Patent number
US09061013B2

Reaction notes

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