Triethylamine → HCID 68356517, compound

HRID 571818Notes

Reaction equation

HRID 571818 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])=[CH:4][C:3]=1[Cl:22].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)=[CH:4][C:3]=1[Cl:22]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 68356520HCID 68356520, compound

Product 1

HCID 68356517HCID 68356517, compoundYield 77%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of tert-butyl (RS)-2-(4-bromo-3-chlorophenyl)-2-hydroxyethyl(2-hydroxyethyl)carbamate (12.7 g) and triethylamine (6.72 ml) in THF (150 ml) at 0-5° C. was added dropwise methanesulfonyl chloride (2.76 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 (28.4 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 dilute aq. HCl, water and saturated brine. The organic phase was dried over Na2SO4 and concentrated in vacuo. The residue was purified by flash column chromatography (silica gel; gradient: 0% to 50% EtOAc in hexanes) to afford tert-butyl (RS)-2-(4-bromo-3-chlorophenyl)morpholine-4-carboxylate (9.32 g, 77%) as a yellow oil. MS (ISP): 324.0 ([{81Br37Cl}M+H—C4H8]+), 321.9 ([{79Br37Cl/81Br35Cl}M+H—C4H8]+), 319.8 ([{79Br35Cl}M+H—C4H8]+).

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 (28.4 ml, 1.7 M solution in toluene) was added
  8. stirringThe reaction mixture was stirred at room temperature for 30 min
  9. additionpoured into EtOAc
  10. extractionextracted sequentially with dilute aq. HCl, water and saturated brine
  11. dry with materialThe organic phase was dried over Na2SO4
  12. concentrationconcentrated in vacuo
  13. customThe residue was purified by flash column chromatography (silica gel; gradient: 0% to 50% EtOAc in hexanes)

Sources & evidence

ORD record
ord-9daaeb6ab872436f927d552755988af2
Source dataset
uspto-grants-2015_05
Patent number
US09029370B2

Reaction notes

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