Methanesulfonyl chloride → HCID 59253289, compound

HRID 1802391Notes

Reaction equation

HRID 1802391 reaction equation
Cl.[CH2:2]([O:4][C:5](=[O:16])[C:6]([CH3:15])([S:8][CH:9]1[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]1)[CH3:7])[CH3:3].C(N(CC)C(C)C)(C)C.[CH3:26][S:27](Cl)(=[O:29])=[O:28]>C1COCC1>[CH2:2]([O:4][C:5](=[O:16])[C:6]([S:8][CH:9]1[CH2:10][CH2:11][N:12]([S:27]([CH3:26])(=[O:29])=[O:28])[CH2:13][CH2:14]1)([CH3:15])[CH3:7])[CH3:3]

Participants

5

Reactant 3

HCID 31297Methanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 67122979HCID 67122979, compound

Product 1

HCID 59253289HCID 59253289, compoundYield 42%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 4.47 g (16.74 mmol) of 2-methyl-2-(piperidin-4-ylsulfanyl)-propionic acid ethyl ester hydrochloride salt in anhydrous THF (30 mL) are added 13.45 mL (77.36 mmol) of N,N-diisoproylethylamine, followed by 2.98 mL (38.58 mmol) of methanesulfonyl chloride. The reaction mixture is heated for 2 d to 60° C. The mixture is concentrated under reduced pressure and the residue is partitioned between saturated aqueous NaHCO3 solution (75 mL) and ethyl acetate (75 mL). The basic aqueous layer is extracted with ethyl acetate (2×50 mL). The combined organic layer is separated and washed with brine (50 mL), dried over MgSO4 and filtered. The filtrate is concentrated under reduced pressure and the residue is purified by column chromatography (silica, eluent: heptanes, 30% ethyl acetate) to give 2.17 g of 2-(1-methanesulfonyl-piperidin-4-ylsulfanyl)-2-methyl-propionic acid ethyl ester as a brown solid. Yield: 42%, ES-MS: m/z 310 [M+H]; 1H NMR (500 MHz, CHLOROFORM-d) δ ppm 1.22 (3 H, t, J=7.11 Hz), 1.47 (6 H, s), 1.59-1.69 (2 H, m), 1.92-2.00 (2 H, m), 2.70 (3 H, s), 2.90-2.99 (3 H, m), 3.39-3.47 (2 H, m), 4.10 (2 H, q, J=7.12 Hz)

Workup

  1. temperatureThe reaction mixture is heated for 2 d to 60° C
  2. concentrationThe mixture is concentrated under reduced pressure
  3. customthe residue is partitioned between saturated aqueous NaHCO3 solution (75 mL) and ethyl acetate (75 mL)
  4. extractionThe basic aqueous layer is extracted with ethyl acetate (2×50 mL)
  5. customThe combined organic layer is separated
  6. washwashed with brine (50 mL)
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationThe filtrate is concentrated under reduced pressure
  10. customthe residue is purified by column chromatography (silica, eluent: heptanes, 30% ethyl acetate)

Sources & evidence

ORD record
ord-05f747f3fdb9452bacae8a986c0b165f
Source dataset
uspto-grants-2013_01
Patent number
US08349871B2

Reaction notes

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