Aluminium lithium hydride → (S)-1-Amino-2-(5-bromo-2-fluoro-phenyl)-propan-2-ol

HRID 2196265Notizen

Reaktionsgleichung

[H-].[H-].[H-].[H-].[Li+].[Al+3].[N:7]([CH2:10][C@:11]([C:14]1[CH:19]=[C:18]([Br:20])[CH:17]=[CH:16][C:15]=1[F:21])([OH:13])[CH3:12])=[N+]=[N-]>C1COCC1>[NH2:7][CH2:10][C@:11]([C:14]1[CH:19]=[C:18]([Br:20])[CH:17]=[CH:16][C:15]=1[F:21])([OH:13])[CH3:12]

Komponenten

Reaktionsbedingungen

Temperatur: 2.5 °C

Versuchsvorschrift

To a suspension of LiAlH4 (4.65 g, 122 mmol) in THF (250 ml) was added under argon at 0-5° C. a solution of (S)-1-azido-2-(5-bromo-2-fluoro-phenyl)-propan-2-ol (33.4 g, 122 mmol) dissolved in THF (150 ml) over a period of 30 min. After stirring for 1 h at 0-5° C., the reaction was quenched by careful addition of water (4.7 ml), 4 N NaOH (4.7 ml) and water (14.1 ml) and stirred again for 3 h at 25° C. The white suspension was dried with MgSO4, filtered and concentrated. The solidified product was re-crystallized from TBME-hexane to provide the title compound as beige crystals: 98% ee (Chiralpak AD-H hexane-EtOH 75-25+0.05% NEt3); TLC (CH2Cl2-MeOH 10:1) Rf=0.10; HPLC RtH5=0.558 min; ESIMS: 248, 250 [(M+H)+]; 1H NMR (360 MHz, CDCl3): δ 7.76 (dd, 1H), 7.25 (m, 1H), 6.82 (dd, 1H), 4.16 (br s, 1H), 3.19 (d, 1H), 2.72 (d, 1H), 1.44 (s, 3H), 0.95 (br s, 2H).

Aufarbeitung

customthe reaction was quenched by careful addition of water (4.7 ml), 4 N NaOH (4.7 ml) and water (14.1 ml)
stirringstirred again for 3 h at 25° C
dry with materialThe white suspension was dried with MgSO4
filtrationfiltered
concentrationconcentrated
customThe solidified product was re-crystallized from TBME-hexane

Quellen und Nachweise

ORD-Eintrag: ord-9e60ed1064f84ac4949a7fcafaeeefc8
Quelldatensatz: uspto-grants-2012_12
DOI: 10.6084/m9.figshare.5104873.v1
Patentnummer: US08338413B1

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