Triethylamine → Methanesulfonic acid 2-(2-bromo-5-fluoro-pyridin-4-yl)-2-hydroxy-propyl ester

HRID 474080Notes

Reaction equation

HRID 474080 reaction equation
[Br:1][C:2]1[CH:7]=[C:6]([C:8]([OH:12])([CH3:11])[CH2:9][OH:10])[C:5]([F:13])=[CH:4][N:3]=1.C(N(CC)CC)C.[CH3:21][S:22](Cl)(=[O:24])=[O:23]>C(Cl)Cl>[Br:1][C:2]1[CH:7]=[C:6]([C:8]([OH:12])([CH3:11])[CH2:9][O:10][S:22]([CH3:21])(=[O:24])=[O:23])[C:5]([F:13])=[CH:4][N:3]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 866680502-(2-Bromo-5-fluoro-pyridin-4-yl)-propane-1,2-diol

Product 1

HCID 86668051Methanesulfonic acid 2-(2-bromo-5-fluoro-pyridin-4-yl)-2-hydroxy-propyl ester

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a suspension of 2-(2-bromo-5-fluoro-pyridin-4-yl)-propane-1,2-diol (17.45 g, 69.8 mmol) and triethylamine (19.45 ml, 14.12 g, 140 mmol) in DCM (350 ml) at 0° C. was added dropwise methanesulfonyl chloride (5.71 ml, 8.39 g, 73.3 mmol) over a period of 10 min. The reaction mixture was stirred at 0° C. for 30 min, then quenched with 1M aq. NaHCO3 soln. The phases were separated, the aq. phase was twice reextracted with DCM and the combined org. phases were washed with brine, dried over Na2SO4, filtered and concentrated. Flash chromatography on silica gel (gradient heptane: EtOAc 0-5 min 88:12, 5-37.5 min 24:76) yielded the title compound as a clear oil. HPLC RtH4=0.76 min; ESIMS: 328, 330 [(M+H)+]; 1H NMR (400 MHz, DMSO-d6): δ 8.22 (d, 1H), 7.82 (d, 1H), 4.58-4.47 (m, 2H), 3.04 (s, 3H), 3.00 (s, 1H), 1.64 (s, 3H).

Workup

  1. customquenched with 1M aq. NaHCO3 soln
  2. customThe phases were separated
  3. washphases were washed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-f45fdd0c97aa4091ac7bfe492f65d452
Source dataset
uspto-grants-2014_01
Patent number
US08637508B2

Reaction notes

Loading…