Sodium Azide → tert-butyl [(1R,2R)-2-azido-3,3-difluorocyclohexyl]carbamate

HRID 2046397Notes

Reaction equation

FC(F)(F)S(O[C@H:7]1[C@H:12]([NH:13][C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:11][CH2:10][CH2:9][C:8]1([F:22])[F:21])(=O)=O.[N-:25]=[N+:26]=[N-:27].[Na+]>CN(C=O)C>[C:17]([O:16][C:14](=[O:15])[NH:13][C@@H:12]1[CH2:11][CH2:10][CH2:9][C:8]([F:22])([F:21])[C@@H:7]1[N:25]=[N+:26]=[N-:27])([CH3:20])([CH3:19])[CH3:18]

Participants

Conditions

Temperature: 100 °C

Procedure

is A solution of (1S,6R)-6-[(tert-butoxycarbonyl)amino]-2,2-difluorocyclohexyl trifluoromethanesulfonate (2.32 g, 6.05 mmol) and sodium azide (2.36 g, 36.3 mmol) in DMF was sealed and heated to 100° C. for 3 hours in a microwave reactor. The reaction was partitioned between water and ethyl acetate. The organics were washed with water, dried over magnesium sulfate, filtered and evaporated in vacuo. Purification by flash chromatography afforded the title compound as a white solid: 1H NMR (500 MHz, CDCl3) δ 4.75 (m, 1H); 3.98 (br s, 1H); 3.88 (m, 1H); 1.96 (m, 2H); 1.70 (m, 2H); 1.46 (s, 9H); 1.37 (m, 2H). tert-Butyl[(1R,6S)-6-azido-2,2-difluorocyclohexyl]carbamate was also obtained from this procedure: 1H NMR (500 MHz, CDCl3) 4.82-4.80 (d, 1H); 3.93-3.89 (dt, 1H); 3.31-3.27 (m, 1H); 2.24-2.19 (m, 1H); 2.13-2.10 (m, 1H); 1.86-1.67 (m, 2H); 1.55-1.52 (m, 2H); 1.48-1.41 (m, 11H). 19F NMR (CDCl3, 564 MHz) −102.2-−102.7 (d, 1F); −113.9-−114.5 (m, 1F).

Workup

customwas sealed
customThe reaction was partitioned between water and ethyl acetate
washThe organics were washed with water
dry with materialdried over magnesium sulfate
filtrationfiltered
customevaporated in vacuo
customPurification by flash chromatography

Sources & evidence

ORD record: ord-06c002f508c44fbfad1dec3206fe19a1
Source dataset: uspto-grants-2013_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08592425B2

Reaction notes

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