Triethylamine → HCID 86672014, compound

HRID 473830Notes

Reaction equation

HRID 473830 reaction equation
[CH3:1][S:2](Cl)(=[O:4])=[O:3].[F:6][C:7]1[CH:8]=[C:9]([C@H:14]2[CH2:19][C@@H:18]([OH:20])[CH2:17][CH2:16][N:15]2[C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH:10]=[CH:11][C:12]=1[F:13].C(OC(OC(C)(C)C)=O)(OC(C)(C)C)=O.C(N(CC)CC)C>O1CCCC1>[F:6][C:7]1[CH:8]=[C:9]([C@H:14]2[CH2:19][C@@H:18]([O:20][S:2]([CH3:1])(=[O:4])=[O:3])[CH2:17][CH2:16][N:15]2[C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH:10]=[CH:11][C:12]=1[F:13]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 90495Di-tert-butyl dicarbonateHCID 86672015HCID 86672015, compound

Product 1

HCID 86672014HCID 86672014, compoundYield 102.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Methanesulfonyl chloride (1.0 g, 3.2 mmol) was added to a mixture of (±)-1,1-dimethylethyl (2R,4S)-2-(3,4-difluorophenyl)-4-hydroxypiperidine-1-carboxylate (1.00 g, 3.0 mmol) (obtained by conducting reagent preparation 28 in the presence of di-tert-butyl dicarbonate) and triethylamine (0.70 g, 7.0 mmol), in tetrahydrofuran (25 mL) at 0° C., and the resulting mixture was at room temperature for two hours. The reaction mixture was then quenched with a cold mixture of water and ethyl acetate. The organic portion was separated, washed with 5% sodium hydroxide, 0.5M hydrochloric acid, water then brine, dried over sodium sulfate, filtered and concentrated. The residue was purified by silica gel chromatography (5% to 75% ethyl acetate in hexanes gradient) to give (±)-1,1-dimethylethyl (2R,4S)-2-(3,4-difluorophenyl)-4-[(methylsulfonyl)oxy]piperidine-1-carboxylate (1.2 g, 88% yield). MS (EI) for C17H23F2NO5S: 392 (MH+).

Workup

  1. customobtained
  2. customThe reaction mixture was then quenched with a cold mixture of water and ethyl acetate
  3. customThe organic portion was separated
  4. washwashed with 5% sodium hydroxide, 0.5M hydrochloric acid, water
  5. dry with materialbrine, dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by silica gel chromatography (5% to 75% ethyl acetate in hexanes gradient)

Sources & evidence

ORD record
ord-63f5c0140431465aa6e2cb9dd3195d2f
Source dataset
uspto-grants-2014_01
Patent number
US08637499B2

Reaction notes

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