Sodium Azide → (2S,4R)-tert-butyl 2-(azidomethyl)-4-hydroxypyrrolidine-1-carboxylate

HRID 240463Notes

Reaction equation

[OH:1][C@H:2]1[CH2:6][N:5]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[C@H:4]([CH2:14]OS(C2C=CC(C)=CC=2)(=O)=O)[CH2:3]1.[N-:26]=[N+:27]=[N-:28].[Na+]>CN(C)C=O>[N:26]([CH2:14][C@@H:4]1[CH2:3][C@@H:2]([OH:1])[CH2:6][N:5]1[C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])=[N+:27]=[N-:28]

Participants

Conditions

Temperature: 55 °C

Procedure

To a solution of Example 220A (365 mg, 1.021 mmol) in N,N-dimethylformamide (5 mL) was added sodium azide (531 mg, 8.17 mmol). The reaction mixture was stirred at 55° C. for 8 hours. Chromatography on a 12 g silica gel column eluted with 5% ethyl acetate/hexanes for 3 minutes followed by a gradient to 100% ethyl acetate over 20 minutes provided the title compound (135 mg, 0.557 mmol, 54.6% yield) as an oil. 1H NMR (400 MHz, DMSO-d6) δ ppm 4.65 (d, J=3.5 Hz, 1H), 4.24 (d, J=3.5 Hz, 1H), 3.97 (ddd, J=10.2, 7.6, 3.1 Hz, 1H), 3.64 (dd, J=12.3, 5.5 Hz, 1H), 3.39-3.22 (m, 3H), 2.01-1.80 (m, 2H), 1.42 (s, 9H); MS (DCI) m/z 243 (M+H)+.

Workup

washChromatography on a 12 g silica gel column eluted with 5% ethyl acetate/hexanes for 3 minutes
waitfollowed by a gradient to 100% ethyl acetate over 20 minutes

Sources & evidence

ORD record: ord-f07c9e9fb4c4424a8672b9fdfa578aae
Source dataset: uspto-grants-2014_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08648074B2

Reaction notes

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