Triethylamine → (2R,3S)-3-azido-1-(2-fluoro-2-methylpropylamino)-4-(4-methoxyphenyl)butan-2-ol

HRID 528693Notes

Reaction equation

Cl.[F:2][C:3]([CH3:7])([CH3:6])[CH2:4][NH2:5].C(N(CC)CC)C.[N:15]([C@H:18]([C@H:28]1[CH2:30][O:29]1)[CH2:19][C:20]1[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[CH:22][CH:21]=1)=[N+:16]=[N-:17]>CC(O)C>[N:15]([C@@H:18]([CH2:19][C:20]1[CH:21]=[CH:22][C:23]([O:26][CH3:27])=[CH:24][CH:25]=1)[C@H:28]([OH:29])[CH2:30][NH:5][CH2:4][C:3]([F:2])([CH3:7])[CH3:6])=[N+:16]=[N-:17]

Participants

Conditions

Temperature: 60 °C

Procedure

To a solution of 2-fluoro-2-methylpropan-1-amine-HCl (2.0 eq) and triethyl amine (4.0 eq) in iPrOH was added an iPrOH solution of (S)-2-((S)-1-azido-2-(4-methoxyphenyl)ethyl)oxirane. The mixture was heated at 60° C. for 6 h. Upon completion the reaction mixture was concentrated then dissolved in ethyl acetate and washed with H2O. The organic layer was combined washed with brine, dried over sodium sulfate and concentrated under vacuum. The residue was purified by flash chromatography. 50% yield. 1H NMR (400 MHz, Chloroform-d) δ 7.4 (d, J=8.4 Hz, 2H), 6.89 (d, J=8.4 Hz, 2H), 3.80 (s, 3H), 3.64-3.57 (m, 2H), 2.96-2.88 (m, 2H), 2.78-2.68 (m, 4H), 1.42 (d, J=3.1 Hz, 3H), 1.37 (d, J=3.1 Hz, 3H).

Workup

concentrationUpon completion the reaction mixture was concentrated
dissolutionthen dissolved in ethyl acetate
washwashed with H2O
washThe organic layer was combined washed with brine
dry with materialdried over sodium sulfate
concentrationconcentrated under vacuum
customThe residue was purified by flash chromatography

Sources & evidence

ORD record: ord-673e5567d3234c43ab2f13edfb1d769a
Source dataset: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09346820B2

Reaction notes

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