Sodium Azide → (S)-tert-butyl 1-azido-3-cyclohexylpropan-2-ylcarbamate

HRID 2355335Notes

Reaction equation

CS(O[CH2:6][C@@H:7]([NH:15][C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:8][CH:9]1[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]1)(=O)=O.[N-:23]=[N+:24]=[N-:25].[Na+]>CN(C=O)C>[N:23]([CH2:6][C@@H:7]([NH:15][C:16](=[O:17])[O:18][C:19]([CH3:22])([CH3:21])[CH3:20])[CH2:8][CH:9]1[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]1)=[N+:24]=[N-:25]

Participants

Conditions

Temperature: 50 °C

Procedure

(S)-2-(tert-Butoxycarbonylamino)-3-cyclohexylpropyl methanesulfonate (13.3 g, 39.3 mmol) from Step 1 was dissolved in anhydrous DMF (140 mL). Solid NaN3 (5.18 g, 79.7 mmol) was added and the reaction was warmed to 50° C. for 5 h. The reaction mixture was permitted to cool to rt and the solvent was removed under reduced pressure (150 Torr, 55° C.). This material was taken up into Et2O (150 mL), washed with water (3×10 mL) and brine (3×10 mL), dried (Na2SO4), decanted, and stripped to give 13.9 g crude product. This was separated on a silica column using a gradient from 0-100% EtOAc in hexanes. Solvent was stripped from appropriate fractions to give (S)-tert-butyl 1-azido-3-cyclohexylpropan-2-ylcarbamate (7.21 g, 65%) as a clear oil. 1H NMR (CDCl3) δ 0.60-1.80 (m 12H), 1.40 (s, 9H), 2.86 (d, 1H), 3.29 (d, 1H), 4.85 (d, 1H), 4.51 (m, 1H), 8.00 (s, 1H). MS ESI+ve m/z 183 (M(−BOC)+1).

Workup

temperatureto cool to rt
customthe solvent was removed under reduced pressure (150 Torr, 55° C.)
washwashed with water (3×10 mL) and brine (3×10 mL)
dry with materialdried (Na2SO4)
customdecanted
customto give 13.9 g crude product
customThis was separated on a silica column

Sources & evidence

ORD record: ord-a8555504b0354a39bc6e2bb92330c757
Source dataset: uspto-grants-2010_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07754737B2

Reaction notes

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