Aluminium lithium hydride → HCID 57794729, compound

HRID 2099269Notes

Reaction equation

[H-].[Al+3].[Li+].[H-].[H-].[H-].[C:7]1([C@:13]2([C:25]#[N:26])[CH2:15][C@H:14]2[CH2:16][O:17][CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1>C(OCC)C>[C:7]1([C@:13]2([CH2:25][NH2:26])[CH2:15][C@H:14]2[CH2:16][O:17][CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=1

Participants

Conditions

Temperature: 0 °C

Procedure

To 16.2 mL 1M lithium aluminum hydride (16.2 mmol) in diethyl ether at 0° C. (1S,2R)-1-phenyl-2-{[(phenylmethyl)oxy]methyl}cyclopropanecarbonitrile (4.25 g, 16.2 mmol), accessed via the method of Preparation 3A, dissolved in 17 mL diethyl ether. After complete addition, the reaction mixture was stirred at 0° C. for 2 h followed by 4 h at ambient temperature. The reaction mixture was diluted with 360 mL diethyl ether and quenched with successive addition of 0.6 mL water, 0.6 mL 15% NaOH, and 3.0 mL water. The reaction mixture was filtered and the filtrate was concentrated to a clear oil. The oil was purified by flash chromatography (SiO2, 3→5% CH3OH/EtOAc with 1% NH4OH) to give the title product (3.08 g, 11.5 mmol, 71%) as a single diastereomer. 1H NMR (300 MHz, CDCl3) δ 7.37-7.19 (m, 10H), 4.62-4.54 (m, 2H), 3.88 (m, 1H), 3.34 (m, 1H), 2.96 (d, J=14.1 Hz, 1H), 2.70 (d, J=14.1 Hz, 1H), 1.58 (m, 1H), 1.00 (m, 1H), 0.62 (m, 1H). ES-LCMS m/z 268.4 (M+H).

Workup

additionAfter complete addition
waitfollowed by 4 h at ambient temperature
customquenched with successive addition of 0.6 mL water, 0.6 mL 15% NaOH, and 3.0 mL water
filtrationThe reaction mixture was filtered
concentrationthe filtrate was concentrated to a clear oil
customThe oil was purified by flash chromatography (SiO2, 3→5% CH3OH/EtOAc with 1% NH4OH)

Sources & evidence

ORD record: ord-2172fa90899a4900a73300015dc414d8
Source dataset: uspto-grants-2009_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07569579B2

Reaction notes

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