Dimethyl Sulfoxide → tert-Butyl (3R)-3-formylpiperidine-1-carboxylate

HRID 1435151Notes

Reaction equation

CS(C)=O.C(Cl)(=O)C(Cl)=O.[OH:11][CH2:12][C@@H:13]1[CH2:18][CH2:17][CH2:16][N:15]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:14]1.C(N(CC)CC)C>ClCCl.[Cl-].[Na+].O>[CH:12]([C@@H:13]1[CH2:18][CH2:17][CH2:16][N:15]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:14]1)=[O:11]

Participants

Conditions

Temperature: -78 °C

Procedure

DMSO (3.3 ml, 46.6 mmol, 2.2 eq) in dichloromethane (20 ml) is added dropwise to a solution of oxalyl chloride (2.03 ml, 23.2 mmol, 1.1 eq) in dichloromethane (80 ml) cooled to −78° C. This mixture is stirred for 10 mins and then tert-butyl (3R)-3-(hydroxymethyl)piperidine-1-carboxylate (4.56 g, 21.1 mmol, 1 eq) in dichloromethane (20 ml) is added dropwise. This is stirred for 20 mins and then triethylamine (15.0 ml, 105 mmol, 5 eq) is added in one portion and then warmed to room temperature over 30 mins. The solution is poured onto diethyl ether (300 ml) and brine (300 ml), separated and the aqueous layer is extracted with diethyl ether (2×100 ml). The organic layers are combined, washed with brine (100 ml), dried over magnesium sulphate, filtered and concentrated in vacuo to give tert-butyl (3R)-3-formylpiperidine-1-carboxylate (4.33 g, 96%) 1H NMR (300 MHz, CDCl3) δH 9.63 (1H, s), 3.75-3.98 (1H, m), 3.48-3.66 (1H, m), 3.16-3.34 (1H, m), 2.90-3.11 (1H, m), 2.26-2.44 (1H, m), 1.79-1.97 (1H, m), 1.53-1.70 (2H, m) and 1.20-1.49 (10H, m).

Workup

stirringThis is stirred for 20 mins
temperaturewarmed to room temperature over 30 mins
customseparated
extractionthe aqueous layer is extracted with diethyl ether (2×100 ml)
washwashed with brine (100 ml)
dry with materialdried over magnesium sulphate
filtrationfiltered
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-7b50d5076de64e58a37c804b4161151c
Source dataset: uspto-grants-2009_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07615648B2

Reaction notes

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