Triethylamine → HCID 68356517, compound

HRID 2403316Notes

Reaction equation

HRID 2403316 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 60 min 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 washed sequentially with dilute aq. HCl, water and saturated brine. The organic phase was separated and was then 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 ([{81Br35Cl or 79Br37Cl}M+H—C4H8]+), 319.9 ([{79Br35Cl}M+H—C4H8]+), 279.9 ([{81Br37Cl}M+H—C4H8—CO2]+), 277.9 ([{81Br35Cl or 79Br37Cl}M+H]—C4H8]—CO2]+), 276.0 ([{79Br35Cl}M+H—C4H8—CO2]+).

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. washwashed sequentially with dilute aq. HCl, water and saturated brine
  11. customThe organic phase was separated
  12. dry with materialwas then dried over Na2SO4
  13. concentrationconcentrated in vacuo
  14. customThe residue was purified by flash column chromatography (silica gel; gradient: 0% to 50% EtOAc in hexanes)

Sources & evidence

ORD record
ord-20c6b7dce19c445cbe2fd9def61cd336
Source dataset
uspto-grants-2014_08
Patent number
US08802673B2

Reaction notes

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