Triethylamine → Tert-butyl 3-(azidomethyl)-4-(tert-butyldimethylsilyloxy)piperidine-1-carboxylate

HRID 57544Notes

Reaction equation

HRID 57544 reaction equation
[Si:1]([O:8][CH:9]1[CH2:14][CH2:13][N:12]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:11][CH:10]1[CH2:22]O)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].C(N(CC)CC)C.CS(Cl)(=O)=O.[N-:36]=[N+:37]=[N-:38].[Na+]>ClCCl.C(OCC)C.CCOC(C)=O>[N:36]([CH2:22][CH:10]1[CH:9]([O:8][Si:1]([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2])[CH2:14][CH2:13][N:12]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:11]1)=[N+:37]=[N-:38]

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 33557Sodium AzideHCID 71113418Tert-butyl 4-[tert-butyl(dimethyl)silyl]oxy-3-(hydroxymethyl)piperidine-1-carboxylate

Product 1

HCID 71113754Tert-butyl 3-(azidomethyl)-4-(tert-butyldimethylsilyloxy)piperidine-1-carboxylate

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of tert-butyl 4-(tert-butyldimethylsilyloxy)-3-(hydroxymethyl)piperidine-1-carboxylate from step B in dichloromethane (50 mL) was added triethylamine (6.06 g, 60 mmol) and methanesulfonyl chloride (3.43 g, 30 mmol) at 0° C. The reaction mixture was allowed to stir at room temperature for 1.5 hours. The crude mixture was diluted with diethyl ether, washed with sat. aq. sodium bicarbonate, brine, then dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. The crude residue was dissolved in NMP (30 mL). Sodium azide (3.90 g, 60 mmol) was added in and the resulting suspension was stirred at 80° C. overnight. The reaction mixture was diluted with EtOAc and hexanes, washed with water, brine, then dried over anhydrous sodium sulfate, filtered, concentrated to give the crude compound. MS (m/z): 271 (M-Boc+H)+.

Workup

  1. washwashed with sat. aq. sodium bicarbonate, brine
  2. dry with materialdried over anhydrous sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. dissolutionThe crude residue was dissolved in NMP (30 mL)
  6. stirringwas stirred at 80° C. overnight
  7. washwashed with water, brine
  8. dry with materialdried over anhydrous sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-b96147692e1645e299a782c9ca773c34
Source dataset
uspto-grants-2016_09
Patent number
US09434726B2

Reaction notes

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