Hydrochloric Acid → Tert-butyl 4-(1,3-dihydroxypropan-2-yl)piperidine-1-carboxylate

HRID 1922688

Reaction equation

C([O:3][C:4](=O)[CH:5]([CH:11]1[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13][CH2:12]1)[C:6](OCC)=[O:7])C.[Li+].[BH4-].Cl>C1COCC1.C1(C)C=CC=CC=1>[C:20]([O:19][C:17]([N:14]1[CH2:15][CH2:16][CH:11]([CH:5]([CH2:4][OH:3])[CH2:6][OH:7])[CH2:12][CH2:13]1)=[O:18])([CH3:23])([CH3:22])[CH3:21]

Participants

Conditions

Temperature: 60 °C

Procedure

To a solution of 2-(1-(tert-butoxycarbonyl)piperidin-4-yl)malonic acid diethyl ester (14.6 g, 0.043 mol) in anhydrous THF (100 mL) and anhydrous toluene (100 mL), LiBH4 (2.1 g. 0.96 mol) was added portion wise. The resulting mixture was heated at 60° C. for 17 h, then stirred at ambient temperature for 24 h. The reaction mixture was slowly added to aqueous HCl (0.1 M, 350 mL) and then extracted with EtOAc. The organic layer was separated and washed with brine, then dried (MgSO4) and concentrated in vacuo. The resultant residue was purified by flash chromatography (Si—PPC, EtOAc: MeOH 100:0 to 98:2 to 95:5 to 90:10 to 80:20) to afford the title compound as a colourless oil (6.91 g, 63%). 1H NMR (CDCl3, 400 MHz) δ 3.90-3.75 (m, 4H); 2.75-2.58 (m, 4H); 1.77-1.61 (m, 4H); 1.52 (m, 1H); 1.45 (s, 9H) and 1.26-1.13 (m, 1H).

Workup

extractionextracted with EtOAc
customThe organic layer was separated
washwashed with brine
dry with materialdried (MgSO4)
concentrationconcentrated in vacuo
customThe resultant residue was purified by flash chromatography (Si—PPC, EtOAc: MeOH 100:0 to 98:2 to 95:5 to 90:10 to 80:20)

Sources & evidence

ORD record: ord-0d3a5261dc704f0a9abba3918781ca8b
Source dataset: uspto-grants-2012_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08173650B2

Linked notes

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