Acetic Acid → HCID 18972703, compound

HRID 1376432Notes

Reaction equation

HRID 1376432 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[NH:10][C:9](=[O:11])[O:8][C:7]([C:16]#[CH:17])([C:12]([F:15])([F:14])[F:13])[C:6]=2[CH:18]=1.[NH:19]1[CH2:23][CH2:22][CH2:21][CH2:20]1.C=O.[C:26](O)(=O)C>[Cu]Cl.O1CCOCC1>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[NH:10][C:9](=[O:11])[O:8][C:7]([C:12]([F:13])([F:14])[F:15])([C:16]#[C:17][CH2:26][N:19]3[CH2:23][CH2:22][CH2:21][CH2:20]3)[C:6]=2[CH:18]=1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 712FormaldehydeHCID 31268PyrrolidineHCID 477134HCID 477134, compound

Product 1

HCID 18972703HCID 18972703, compoundYield 71.7%

Reagents, catalysts & solvents 2

HCID 62652Cuprous chlorideCatalystHCID 312751,4-DioxaneSolvent

Procedure

A dioxane solution of (+/-)6-chloro-4-ethynyl-4-(1,1,1-trifluoromethyl)-1,4-dihydro-2H-3,1-benzoxazin-2-one (150 mg, 0.544 mmol), pyrrolidine (52.2 μL, 0.626 mmol), paraformaldehyde (20.5 mg, 0.681 mmol), acetic acid (31.1 μL, 0.544 mmol) and copper (I) chloride (20.5 mg, 0.207 mmol in 3.5 ml dioxane) was heated to 50° C. in an oil bath for approximately 2 h. The reaction mixture was quenched into 2N HCl and extracted with ethyl acetate. The aqueous layer was neutralized with solid potassium carbonate and extracted with ethyl acetate (3x). The combined extracts were washed with water and brine before drying over sodium sulfate to afford 140 mg crude product. Chromatographic purification on silica gel and recrystallization from ethyl acetate: hexane afforded crystalline (+/-) 6-chloro-4-(1,1,1-trifluoromethyl)-4-[(3-(1-pyrrolidinyl))-1-propynyl]-1,4-dihydro-2H-3,1-benzoxazin-2-one (89 mg, 46% yield): MP 160°-161° C. (dec). 1H-NMR (CDCl3): δ1.85-1.89 (m, 4H), 2.68-2.71 (m, 4H), 3.67 (s, 1H), 6.88 (d, J=8.55 Hz, 1H), 7.40 (dd, J=2.19, 8.54 Hz, 1H), 7.55 (s, 1H), 9.45 (s, 1H).

Workup

  1. customThe reaction mixture was quenched into 2N HCl
  2. extractionextracted with ethyl acetate
  3. extractionextracted with ethyl acetate (3x)
  4. washThe combined extracts were washed with water and brine
  5. dry with materialbefore drying over sodium sulfate

Sources & evidence

ORD record
ord-cce39019514b4b8c84f4f617e269c48f
Source dataset
uspto-grants-1997_09
Patent number
US05663169

Reaction notes

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