Trifluoroacetic acid → HCID 178422394, compound

HRID 1375187Notes

Reaction equation

HRID 1375187 reaction equation
[CH3:1][C:2]1[CH:11]=[CH:10][C:5]2[C:6]([OH:9])=[N:7][O:8][C:4]=2[CH:3]=1.C(O)(C(F)(F)F)=O.[Cl:19]N1CCOCC1>CCOC(C)=O>[Cl:19][C:11]1[C:2]([CH3:1])=[CH:3][C:4]2[O:8][N:7]=[C:6]([OH:9])[C:5]=2[CH:10]=1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 90067Morpholine, 4-chloro-HCID 178422984HCID 178422984, compound

Product 1

HCID 178422394HCID 178422394, compound

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

A 25 ml round-bottom flask equipped with a stir bar was charged with 6-methyl-benzo[d]isoxazol-3-ol (298 mg, 2.0 mmole, 1.0 eq) and TFA (2.0 ml) and cooled to 0° C. in an ice bath. Neat N-chloromorpholine (242 μL, 2.0 mmoles, 1.0 eq, Organic Syntheses, CV 8, 167) was added dropwise and the reaction mixture was allowed to warm to room temperature over the period of 30 minutes. EtOAc was added, the crude product was partitioned in a separatory funnel (EtOAc/1.0M aqueous HCl), the organic layer was dried with MgSO4 and excess solvent was removed from the filtrate in vacuo. Crystallization of the crude product (383 mg) from a mixture of 20 ml of toluene and 6 ml of EtOAc provided 206 mg (94% purity determined by HPLC) as a white solid. (1H DMSO-d6, 400 MHz) δ 12.41 (s, 1H), 7.77 (s, 1H), 7.59 (s, 1H), 2.43 (s, 3H); (13C DMSO-d6, 100 MHz) δ 164.46, 161.87, 138.53, 128.08, 120.59, 113.78, 111.83, 20.49.

Workup

  1. customA 25 ml round-bottom flask equipped with a stir bar
  2. temperatureto warm to room temperature over the period of 30 minutes
  3. customthe crude product was partitioned in a separatory funnel (EtOAc/1.0M aqueous HCl)
  4. dry with materialthe organic layer was dried with MgSO4 and excess solvent
  5. customwas removed from the filtrate in vacuo
  6. customCrystallization of the crude product (383 mg)
  7. additionfrom a mixture of 20 ml of toluene and 6 ml of EtOAc
  8. customprovided 206 mg (94% purity determined by HPLC) as a white solid

Sources & evidence

ORD record
ord-52f9707a56f14735bec4d74bf0c2cdeb
Source dataset
uspto-grants-2007_01
Patent number
US07166725B2

Reaction notes

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