Benzyl 4-formylpiperidine-1-carboxylate → Phenylmethyl 4-(1-hydroxyethyl)-1-piperidinecarboxylate

HRID 423597Notes

Reaction equation

[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][CH:14]([CH:17]=[O:18])[CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:19][Mg]Br>CCOCC>[OH:18][CH:17]([CH:14]1[CH2:15][CH2:16][N:11]([C:9]([O:8][CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)=[O:10])[CH2:12][CH2:13]1)[CH3:19]

Participants

Conditions

Temperature: -78 °C

Procedure

A solution of N-(benzyloxycarbonyl)-4-formyl-piperidine (1 g, 3.92 mmol) in Et2O (40 mL) at −78° C. was treated with methylmagnesium bromide (3M in Et2O, 3.2 mL, 9.60 mmol). The reaction mixture was stirred at −78° C. for 2 h, quenched with saturated aqueous NH4Cl and extracted with Et2O. The combined organic extract was washed with brine and dried over Na2SO4, filtered, and the filtrate was concentrated to a colorless oil. The crude product was purified by flash chromatography on an ISCO silica gel column using 0 to 70% EtOAc/hexanes to give 0.64 g (62%) of (±)-phenylmethyl 4-(1-hydroxyethyl)-1-piperidinecarboxylate as a colorless oil. 1H NMR (400 MHz, CDCl3): δ 7.40-7.25 (m, 5H), 5.11 (s, 2H), 4.30-4.15 (m, 2H), 3.65-3.55 (m, 1H), 2.80-2.65 (m, 2H), 1.90-1.80 (m, 1H), 1.80-1.70 (m, 1H), 1.70-1.55 (m, 1H), 1.30-1.10 (m, 5H).

Workup

customquenched with saturated aqueous NH4Cl
extractionextracted with Et2O
extractionThe combined organic extract
washwas washed with brine
dry with materialdried over Na2SO4
filtrationfiltered
concentrationthe filtrate was concentrated to a colorless oil
customThe crude product was purified by flash chromatography on an ISCO silica gel column

Sources & evidence

ORD record: ord-ccaa042c41c54b1580f1e0f695bb0f45
Source dataset: uspto-grants-2012_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08101634B2

Reaction notes

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