Methanesulfonyl chloride → HCID 86672010, compound

HRID 473821Notes

Reaction equation

HRID 473821 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]2[CH2:13][C@H:12]([OH:14])[CH2:11][CH2:10][N:9]2[C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])=[CH:4][CH:3]=1.[CH3:22][S:23](Cl)(=[O:25])=[O:24].C(N(C(C)C)CC)(C)C>O1CCCC1.CN(C)C1C=CN=CC=1.C(OCC)(=O)C>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C@@H:8]2[CH2:13][C@H:12]([O:14][S:23]([CH3:22])(=[O:25])=[O:24])[CH2:11][CH2:10][N:9]2[C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])=[CH:6][CH:7]=1

Participants

7

Reactant 3

HCID 31297Methanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 70815153HCID 70815153, compound

Product 1

HCID 86672010HCID 86672010, compoundYield 88%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To (±)-(2S,4R)-tert-butyl 2-(4-fluorophenyl)-4-hydroxypiperidine-1-carboxylate (0.55 g, 1.90 mmol) in tetrahydrofuran (20 mL) was added methanesulfonyl chloride (0.158 mL, 2.05 mmol), followed by dropwise addition of diisopropylethylamine (0.50 g, 3.9 mmol) and N,N-dimethylpyridin-4-amine (10 mg). After 30 minutes the reaction was diluted with ethyl acetate (50 mL) and washed with 0.1 M hydrochloric acid (25 mL) then saturated sodium bicarbonate (50 mL), dried over anhydrous sodium sulfate, filtered and concentrated. The residue was purified by silica gel chromatography (ethyl acetate:hexanes, 1:4) to give (±)-(2S,4R)-tert-butyl 2-(4-fluorophenyl)-4-(methylsulfonyloxy)piperidine-1-carboxylate (0.62 g, 88% yield). 1H NMR (400 MHz, CDCl3): 7.19 (dd, 1H), 7.05 (t, 2H), 5.38 (d, 1H), 5.14 (m, 1H), 4.14 (m, 1H), 3.25 (m, 1H), 2.68 (m, 1H), 2.59 (s, 3H), 2.21 9M, 1H), 1.93 (m, 2H), 1.42 (s, 9H).

Workup

  1. washwashed with 0.1 M hydrochloric acid (25 mL)
  2. dry with materialsaturated sodium bicarbonate (50 mL), dried over anhydrous sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe residue was purified by silica gel chromatography (ethyl acetate:hexanes, 1:4)

Sources & evidence

ORD record
ord-9acf651d87714c5abd5c502bcee21ebe
Source dataset
uspto-grants-2014_01
Patent number
US08637499B2

Reaction notes

Loading…