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

HRID 1665264Notes

Reaction equation

HRID 1665264 reaction equation
[O:1]1[C:3]2([CH2:8][CH2:7][N:6]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:5][CH2:4]2)[CH2:2]1.C1([Si](C2C=CC=CC=2)(C2C=CC=CC=2)[SH:23])C=CC=CC=1.C(N(CC)CC)C>CO>[OH:1][C:3]1([CH2:2][SH:23])[CH2:8][CH2:7][N:6]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:5][CH2:4]1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 621128TriphenylsilanethiolHCID 22135564tert-Butyl 1-oxa-6-azaspiro(2.5)octane-6-carboxylate

Product 1

HCID 53438219Tert-butyl 4-hydroxy-4-(mercaptomethyl)piperidine-1-carboxylateYield 808.6%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a mixture of tert-butyl 1-oxa-6-azaspiro[2.5]octane-6-carboxylate (35.3 g, 16.55 mmol) and triphenylsilanethiol (48.4 g, 16.55 mmol) in anhydrous methanol (1.0 L) was added triethylamine (23.1 ml, 16.55 mmol) drop-wise over the course of 30 minutes. The reaction was stirred for 1 hour at room temperature and the methanol was evaporated under reduced pressure. The crude product was purified by flash column chromatography (SiO2, 5% EtOAc in hexanes to 40% EtOAc in hexanes) to afford 81% (33.1 g) pure final product. M.p.=54-55° C.; 400 MHz 1H NMR (CDCl3) δ: 3.97-3.78 (m, 2H), 3.19-3.08 (m, 2H), 2.61 (d, J=4.4 Hz, 2H), 1.70-1.55 (m, 2H), 1.50-1.38 (m, 11H); LCMS: 248 [M+H].

Workup

  1. customthe methanol was evaporated under reduced pressure
  2. customThe crude product was purified by flash column chromatography (SiO2, 5% EtOAc in hexanes to 40% EtOAc in hexanes)

Sources & evidence

ORD record
ord-8bff38802e9a46778701ea53290dd38b
Source dataset
uspto-grants-2011_10
Patent number
US08039503B2

Reaction notes

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