Triethylamine → HCID 68325460, compound

HRID 2403331Notes

Reaction equation

HRID 2403331 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([OH:21])[CH2:9][N:10]([CH2:18][CH2:19]O)[C:11](=[O:17])[O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[C:4]([F:22])[CH:3]=1.C(N(CC)CC)C.CS(Cl)(=O)=O>C1COCC1>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[O:21][CH2:19][CH2:18][N:10]([C:11]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:17])[CH2:9]2)=[C:4]([F:22])[CH:3]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 68325867HCID 68325867, compound

Product 1

HCID 68325460HCID 68325460, compoundYield 44%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of (RS)-tert-butyl 2-(4-bromo-2-fluorophenyl)-2-hydroxyethyl(2-hydroxyethyl)carbamate (15.5 g) and triethylamine (9.85 ml) in THF (120 ml) at 0-5° C. was added dropwise methanesulfonyl chloride (3.35 ml). The reaction mixture was then stirred at room temperature for 1 hour to afford a white suspension. The reaction mixture was then filtered to remove triethylamine hydrochloride, washing the filter with THF (20 ml). The filtrate was cooled to 0-5° C. and potassium 2-methyl-2-butoxide (36.2 ml, 1.7 M solution in toluene) was added. The reaction mixture was stirred at room temperature for 20 min and then poured into EtOAc and washed sequentially with 1 M aq. HCl, water and saturated brine. The organic phase was separated, dried over Na2SO4 and concentrated in vacuo. The residue was purified by flash column chromatography (silica gel; gradient: 0% to 30% EtOAc in hexanes) to afford (RS)-tert-butyl 2-(4-bromo-2-fluorophenyl)morpholine-4-carboxylate (6.46 g, 44%) as a yellow oil. MS (EI): 305 ([{81Br}M-C4H8]+), 303 ([{79Br}M-C4H8]+), 260 ([{∥Br}M-C4H8—CO2H]+), 258 ([{79Br}M-C4H8—CO2H]+).

Workup

  1. customto afford a white suspension
  2. filtrationThe reaction mixture was then filtered
  3. customto remove triethylamine hydrochloride
  4. washwashing the
  5. filtrationfilter with THF (20 ml)
  6. temperatureThe filtrate was cooled to 0-5° C.
  7. additionpotassium 2-methyl-2-butoxide (36.2 ml, 1.7 M solution in toluene) was added
  8. stirringThe reaction mixture was stirred at room temperature for 20 min
  9. additionpoured into EtOAc
  10. washwashed sequentially with 1 M aq. HCl, water and saturated brine
  11. customThe organic phase was separated
  12. dry with materialdried over Na2SO4
  13. concentrationconcentrated in vacuo
  14. customThe residue was purified by flash column chromatography (silica gel; gradient: 0% to 30% EtOAc in hexanes)

Sources & evidence

ORD record
ord-219623b5e59b45b798f92a17ff01221e
Source dataset
uspto-grants-2014_08
Patent number
US08802673B2

Reaction notes

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