Triethylamine → HCID 68356519, compound

HRID 571837Notes

Reaction equation

HRID 571837 reaction equation
O[CH:2]([C:15]1[CH:20]=[CH:19][C:18]([N+:21]([O-:23])=[O:22])=[C:17]([CH3:24])[CH:16]=1)[CH2:3][N:4]([CH2:12][CH2:13][OH:14])[C:5](=[O:11])[O:6][C:7]([CH3:10])([CH3:9])[CH3:8].C(N(CC)CC)C.CS(Cl)(=O)=O>C1COCC1>[CH3:24][C:17]1[CH:16]=[C:15]([CH:2]2[O:14][CH2:13][CH2:12][N:4]([C:5]([O:6][C:7]([CH3:10])([CH3:9])[CH3:8])=[O:11])[CH2:3]2)[CH:20]=[CH:19][C:18]=1[N+:21]([O-:23])=[O:22]

Participants

5

Reactant 3

HCID 8471Triethylamine2×HCID 31297Methanesulfonyl chloride2×HCID 68356512HCID 68356512, compound

Product 1

HCID 68356519HCID 68356519, compoundYield 36%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of tert-butyl (RS)-2-hydroxy-2-(3-methyl-4-nitrophenyl)ethyl(2-hydroxyethyl)carbamate (6.55 g) and triethylamine (3.22 ml) in THF (50 ml) at 0-5° C. was added dropwise methanesulfonyl chloride (1.65 ml). The reaction mixture was then stirred at room temperature for 30 min to afford a yellow suspension. TLC analysis showed a small amount of starting material remaining and so further aliquots of triethylamine (0.5 ml) and methanesulfonyl chloride (0.2 ml) were added. The reaction mixture was stirred at room temperature for a further 20 min and 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 (17.0 ml, 1.7 M solution in toluene) was added. The reaction mixture was stirred at room temperature for 30 min and then poured into EtOAc and extracted sequentially with water and with saturated brine. The organic layer was dried over Na2SO4 and concentrated in vacuo. The residue was purified by flash column chromatography (silica gel; gradient: 0% to 70% EtOAc in hexanes) to afford tert-butyl (RS)-2-(3-methyl-4-nitrophenyl)morpholine-4-carboxylate (2.21 g, 36%) as a yellow oil. MS (ISP): 223.1 ([M+H—O5H8O2]+).

Workup

  1. customto afford a yellow suspension
  2. stirringThe reaction mixture was stirred at room temperature for a further 20 min
  3. filtrationwas then filtered
  4. customto remove triethylamine hydrochloride
  5. washwashing the
  6. filtrationfilter with THF (20 ml)
  7. temperatureThe filtrate was cooled to 0-5° C.
  8. additionpotassium 2-methyl-2-butoxide (17.0 ml, 1.7 M solution in toluene) was added
  9. stirringThe reaction mixture was stirred at room temperature for 30 min
  10. additionpoured into EtOAc
  11. extractionextracted sequentially with water and with saturated brine
  12. dry with materialThe organic layer was dried over Na2SO4
  13. concentrationconcentrated in vacuo
  14. customThe residue was purified by flash column chromatography (silica gel; gradient: 0% to 70% EtOAc in hexanes)

Sources & evidence

ORD record
ord-85c1580e157a4f63a68c6a048377a783
Source dataset
uspto-grants-2015_05
Patent number
US09029370B2

Reaction notes

Loading…