Sodium Bicarbonate → Tert-butyl 4-hydroxy-4-(mercaptomethyl)piperidine-1-carboxylate

HRID 1665265Notes

Reaction equation

HRID 1665265 reaction equation
[Na].O.C1(C)C=CC([S:9](O)(=O)=O)=CC=1.[O:14]1[C:16]2([CH2:21][CH2:20][N:19]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:18][CH2:17]2)[CH2:15]1.C(=O)(O)[O-].[Na+]>CO>[OH:14][C:16]1([CH2:15][SH:9])[CH2:21][CH2:20][N:19]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:18][CH2:17]1

Participants

6

Reactant 4

HCID 516892Sodium BicarbonateHCID 521998p-Toluenesulfonic acid monohydrateHCID 5360545SodiumHCID 22135564tert-Butyl 1-oxa-6-azaspiro(2.5)octane-6-carboxylate

Product 1

HCID 53438219Tert-butyl 4-hydroxy-4-(mercaptomethyl)piperidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
0 °C

Procedure

Sodium sufide nonahydrate (60 g, 0.25 mol) was dissolved in MeOH (1.25 L), and the resulting solution was degassed by applying vacuumn and filling nitrogen three times. The solution was then cooled to 0° C. with an ice-water bath. To the above solution was added p-toluenesulfonic acid hydrate (76 g, 0.4 mol) and the resulting mixture was stirred at 0° C. for 10 min A yellowish colored solution was formed. The tert-butyl 1-oxa-6-azaspiro[2.5]octane-6-carboxylate (21.2 g, 0.1 mol) was added to the reaction mixture and stirred at 0° C. for 1 h and then at room temperature for 1.5 h. Saturated sodium bicarbonate solution (200 mL) was added to the reaction, and the methanol was evaporated under reduced pressure. To the residue was added water (500 mL) and extracted with EtOAc (1×400 mL and 2×250 mL), the combined organic layer was washed with brine (250 mL) and dried over sodium sulfate. After concentration, the crude product (26.2 g) was obtained as an oil. The crude product was purified by flash column chromatography (SiO2, 5% to 40% EtOAc in hexanes) to afford the product as a white solid. (19.2 g, 78%). M.p.=54-55° C.; 400 MHz 1H NMR (CDCl3) δ: 3.97-3.80 (m, 2H), 3.19-3.08 (m, 2H), 2.61 (d, J=4.4 Hz, 2H), 2.22 (s, 1H), 1.68-1.60 (m, 2H), 1.50-1.40 (m, 11H); LCMS: 248 [M+H].

Workup

  1. customthe resulting solution was degassed
  2. customwas formed
  3. stirringstirred at 0° C. for 1 h
  4. waitat room temperature for 1.5 h
  5. customthe methanol was evaporated under reduced pressure
  6. additionTo the residue was added water (500 mL)
  7. extractionextracted with EtOAc (1×400 mL and 2×250 mL)
  8. washthe combined organic layer was washed with brine (250 mL)
  9. dry with materialdried over sodium sulfate
  10. concentrationAfter concentration
  11. customthe crude product (26.2 g) was obtained as an oil
  12. customThe crude product was purified by flash column chromatography (SiO2, 5% to 40% EtOAc in hexanes)

Sources & evidence

ORD record
ord-13de02f1d0734083bcb8e9e5f8b9d2c4
Source dataset
uspto-grants-2011_10
Patent number
US08039503B2

Reaction notes

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