Triethylamine → HCID 86672012, compound

HRID 473827Notes

Reaction equation

HRID 473827 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]([CH2:20][OH:21])[CH2:17][CH2:16][N:15]2[C:22]([O:24][CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)=[O:23])[CH:10]=[CH:11][C:12]=1[F:13].C(N(CC)CC)C.N12CCN(CC1)CC2>C1(C)C=CC=CC=1>[F:6][C:7]1[CH:8]=[C:9]([C@H:14]2[CH2:19][C@@H:18]([CH2:20][O:21][S:2]([CH3:1])(=[O:4])=[O:3])[CH2:17][CH2:16][N:15]2[C:22]([O:24][CH2:25][C:26]2[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=2)=[O:23])[CH:10]=[CH:11][C:12]=1[F:13]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 9237DabcoHCID 31297Methanesulfonyl chlorideHCID 86672011HCID 86672011, compound

Product 1

HCID 86672012HCID 86672012, compoundYield 96.4%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
0 °C

Procedure

Methanesulfonyl chloride (74 mg, 0.65 mmol) was added to a mixture of (±)-phenylmethyl (2R,4S)-2-(3,4-difluorophenyl)-4-(hydroxymethyl)piperidine-1-carboxylate (233 mg, 0.64 mmol), triethylamine (233 mg, 1.7 mmol), and 1,4-diazabicyclo[2.2.2]octane (15 mg, 0.13 mmol) in toluene (10 mL) at 0° C., and the resulting mixture was stirred at 0° C. for 15 minutes, and at room temperature for another 15 minutes. The reaction mixture was then quenched with a cold mixture of water and ethyl acetate. The organic portion was separated, washed with water, then brine, dried over sodium sulfate, filtered and concentrated. The residue was purified by silica gel chromatography (5% to 25% ethyl acetate in hexanes gradient) to give (±)-phenylmethyl (2R,4S)-2-(3,4-difluorophenyl)-4-{[(methylsulfonyl)oxy]methyl}piperidine-1-carboxylate (271 mg, 96% yield). MS (EI) for C21H23F2NO5S: 440 (MH+).

Workup

  1. waitat room temperature for another 15 minutes
  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 water
  5. dry with materialbrine, dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by silica gel chromatography (5% to 25% ethyl acetate in hexanes gradient)

Sources & evidence

ORD record
ord-a03a33b6b35140629c59b1e8a5803e93
Source dataset
uspto-grants-2014_01
Patent number
US08637499B2

Reaction notes

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