Triethylamine → HCID 86671402, compound

HRID 2403307Notes

Reaction equation

HRID 2403307 reaction equation
[Br:1][C:2]1[N: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[CH3:22].C(N(CC)CC)C.CS(Cl)(=O)=O>C1COCC1>[Br:1][C:2]1[N: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[CH3:22]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 86671401HCID 86671401, compound

Product 1

HCID 86671402HCID 86671402, compoundYield 73%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of tert-butyl (RS)-2-(6-bromo-5-methylpyridin-3-yl)-2-hydroxyethyl(2-hydroxyethyl)carbamate (2.57 g) and triethylamine (1.51 ml) in THF (30 ml) at 0-5° C. was added dropwise methanesulfonyl chloride (546 •1). The reaction mixture was then stirred at room temperature for 15 min to afford a white suspension. The reaction mixture was then filtered to remove triethylamine hydrochloride, washing the filter with THF (10 ml). The filtrate was cooled to 0-5° C. and potassium 2-methyl-2-butoxide (5.62 ml, 1.7 M solution in toluene) was added. The reaction mixture was stirred at room temperature for 10 min and then poured into EtOAc and washed sequentially with water and with 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 70% EtOAc in hexanes) to afford tert-butyl (RS)-2-(6-bromo-5-methylpyridin-3-yl)morpholine-4-carboxylate (1.7 g, 73% over 3 steps) as a colourless oil. MS (ISP): 359.0 ([{81Br}M+H]+), 357.0 ([{79Br}M+H]+), 303.0 ([{81Br}M+H—C4H8]+), 301.0 ([{79Br}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 (10 ml)
  6. temperatureThe filtrate was cooled to 0-5° C.
  7. additionpotassium 2-methyl-2-butoxide (5.62 ml, 1.7 M solution in toluene) was added
  8. stirringThe reaction mixture was stirred at room temperature for 10 min
  9. additionpoured into EtOAc
  10. washwashed sequentially with water and with 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 70% EtOAc in hexanes)

Sources & evidence

ORD record
ord-d4560f862d154d9ab921364834faff4b
Source dataset
uspto-grants-2014_08
Patent number
US08802673B2

Reaction notes

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