Propanal → [2-(2-Hydroxy-butyl)-5-methoxy-phenyl]-carbamic acid t-butyl Ester

HRID 985275Notes

Reaction equation

[C:1]([O:5][C:6](=[O:17])[NH:7][C:8]1[CH:13]=[C:12]([O:14][CH3:15])[CH:11]=[CH:10][C:9]=1[CH3:16])([CH3:4])([CH3:3])[CH3:2].[Li]C(CC)C.[CH:23](=[O:26])[CH2:24][CH3:25]>C1COCC1>[C:1]([O:5][C:6](=[O:17])[NH:7][C:8]1[CH:13]=[C:12]([O:14][CH3:15])[CH:11]=[CH:10][C:9]=1[CH2:16][CH:23]([OH:26])[CH2:24][CH3:25])([CH3:4])([CH3:3])[CH3:2]

Participants

Conditions

Temperature: -20 °C

Procedure

To a solution of (5-methoxy-2-methyl-phenyl)-carbamic acid t-butyl ester (6.95 g, 29.3 mmole) in 100 ml THF cooled at −45° C. was added sec-BuLi (45 ml, 58.5 mmole) slowly to keep temperature lower than −45° C. The reaction mixture was stirred and warmed to −20° C., then cooled to −45° C. and propionaldehyde (2.67 ml, 36.63 mmole) was added. The reaction mixture was stirred and warmed to room temperature for 1 h, quenched with 1N HCl and extracted with EtOAc, dried over MgSO4 and concentrated. The residue was purified by flash column chromatography (10-15% EtOAc in hexane) to give colorless oil (3.40 g, 39%). 1H NMR (CDCl3) δ7.96 (1H, s), 7.44 (1H, s), 6.96-7.00 (1H, m), 6.55 (1H, m), 3.80 (3H, s), 2.60-2.76 (2H, m), 1.93-1.95 (2H, m), 1.50 (9H, s), 0.93-1.01 (4H, m). ESIMS (MNa+): 318.20.

Workup

customlower than −45° C
temperaturecooled to −45° C.
stirringThe reaction mixture was stirred
temperaturewarmed to room temperature for 1 h
customquenched with 1N HCl
extractionextracted with EtOAc
dry with materialdried over MgSO4
concentrationconcentrated
customThe residue was purified by flash column chromatography (10-15% EtOAc in hexane)

Sources & evidence

ORD record: ord-03253676e28d45a7a03b917f3382c473
Source dataset: uspto-grants-2005_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06869962B2

Reaction notes

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