Sodium hydride → 4-(3,5-Di-tert-butyl-4-hydroxy-phenylsulfanyl)-piperidine-1-carboxylic acid tert-butyl ester

HRID 599469Notes

Reaction equation

HRID 599469 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11](OS(C)(=O)=O)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:19]([C:23]1[CH:28]=[C:27]([SH:29])[CH:26]=[C:25]([C:30]([CH3:33])([CH3:32])[CH3:31])[C:24]=1[OH:34])([CH3:22])([CH3:21])[CH3:20].[H-].[Na+]>CN(C=O)C.C(OCC)(=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][CH:11]([S:29][C:27]2[CH:26]=[C:25]([C:30]([CH3:31])([CH3:32])[CH3:33])[C:24]([OH:34])=[C:23]([C:19]([CH3:22])([CH3:21])[CH3:20])[CH:28]=2)[CH2:12][CH2:13]1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 703702,6-Di-tert-butyl-4-mercaptophenolHCID 41848691-(tert-Butoxycarbonyl)-4-(methanesulfonyloxy)piperidine

Product 1

HCID 866354264-(3,5-Di-tert-butyl-4-hydroxy-phenylsulfanyl)-piperidine-1-carboxylic acid tert-butyl esterYield 54.6%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

To 4-methanesulfonyloxy-piperidine-1-carboxylic acid tert-butyl ester (Ex. 3a, 22 g) and 2,6-di-tert-butyl-4-mercapto-phenol (16.58 g) in 300 mL of DMF was added sodium hydride (3.8 g, 60% in oil). The mixture was stirred at 60° C. for 20 h and then poured onto ice and quenched with 1 N HCl. The gooey solid obtained via filtration was dissolved in Ethyl acetate, dried over Na2SO4, and concentrated. The crude product was dissolved in a minimal amount of diethyl ether and triturated with hexanes to give 4-(3,5-di-tert-butyl-4-hydroxy-phenylsulfanyl)-piperidine-1-carboxylic acid tert-butyl ester as an off-white solid (16 g), mp 151-152° C. 1H-NMR (400 MHz, CDCl3): δ 7.28 (s, 2H), 5.28 (s, 1H), 3.98 (s, 2H), 3.03-2.96 (m, 1H), 2.87 (t, 2H, J=10.4 Hz), 1.91-1.87 (m, 2H), 1.54-1.48 (m, 2H), 1.44 (s, 9H), 1.43 (s, 18H). HRMS (ESI) Calcd. for C24H39NO3S: 421.2651 (M+). Found: 421.2656. Anal. Calcd. for C24H39NO3S, C, 68.37; H, 9.32; N, 3.32; S, 7.60. Found: C, 68.20; H, 9.42; N, 3.23; S, 7.77.

Workup

  1. additionpoured onto ice
  2. customquenched with 1 N HCl
  3. customThe gooey solid obtained via filtration
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated
  6. dissolutionThe crude product was dissolved in a minimal amount of diethyl ether
  7. customtriturated with hexanes

Sources & evidence

ORD record
ord-e08c0ce4d92547b58bf02d7a5d458ec5
Source dataset
uspto-grants-2011_03
Patent number
US07897776B2

Reaction notes

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