Sodium Azide → HCID 86762147, compound

HRID 1907409Notes

Reaction equation

HRID 1907409 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([F:25])=[C:6]([C@:8]23[O:16][CH2:15][CH2:14][C@H:13]2[CH2:12][S:11][C:10]([NH:17][C:18](=[O:24])[O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[N:9]3)[CH:7]=1.[N-:26]=[N+:27]=[N-:28].[Na+].[Na].O=C1O[C@H]([C@H](CO)O)C(O)=C1O>C(O)C.O.O.O.O.O.O.S([O-])([O-])(=O)=O.[Cu+2]>[N:26]([C:2]1[CH:3]=[CH:4][C:5]([F:25])=[C:6]([C@:8]23[O:16][CH2:15][CH2:14][C@H:13]2[CH2:12][S:11][C:10]([NH:17][C:18](=[O:24])[O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[N:9]3)[CH:7]=1)=[N+:27]=[N-:28]

Participants

7

Reactant 3

HCID 33557Sodium AzideHCID 66586226sodium L-ascorbic acidHCID 86762146HCID 86762146, compound

Product 1

HCID 86762147HCID 86762147, compoundYield 36.5%

Reagents, catalysts & solvents 3

HCID 24463Copper sulfate pentahydrateCatalystHCID 702EthanolSolventHCID 962WaterSolvent2×

Conditions

Temperature
80 °C

Procedure

A suspension of tert-butyl ((4aR,7aR)-7a-(5-bromo-2-fluorophenyl)-4a,5,6,7a-tetrahydro-4H-furo[2,3-d][1,3]thiazin-2-yl)carbamate (300 mg, 0.696 mmol), sodium azide (274 mg, 4.21 mmol), trans-1,2-(bismethylamino)cyclohexane (0.073 mL, 0.464 mmol), 0.66 M aqueous L-ascorbic acid sodium salt (0.780 mL, 0.515 mmol) and 0.33 M aqueous copper(II) sulfate pentahydrate (0.936 mL, 0.309 mmol) in ethanol (3.6 mL) and water (0.70 mL) was heated to 80° C. for 1 h. Water was added and the aqueous layer was extracted with EtOAc (×3). The combined organic layers were washed with brine, dried over anhydrous sodium sulfate, and filtered, and the filtrate was evaporated in vacuo to give the crude product. The crude product was purified by preparative TLC on silica gel (0.50 mm thickness) eluting with 30% EtOAc/Hexane to give tert-butyl ((4aR,7aR)-7a-(5-azido-2-fluorophenyl)-4a,5,6,7a-tetrahydro-4H-furo[2,3-d][1,3]thiazin-2-yl)carbamate (100 mg, 0.254 mmol, 36.5% yield) as a white foam. 1H NMR (500 MHz, CHLOROFORM-d) δ 7.30-7.24 (m, 1H), 7.09 (dd, J=10.7, 8.7 Hz, 1H), 7.05-6.93 (m, 1H), 4.23-4.02 (m, 2H), 3.29 (d, J=12.7 Hz, 1H), 2.95 (br. s., 2H), 2.45-2.32 (m, 1H), 2.27-2.15 (m, 1H), 1.50 (s, 9H). MS (M−1): 392.2.

Workup

  1. extractionthe aqueous layer was extracted with EtOAc (×3)
  2. washThe combined organic layers were washed with brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. customthe filtrate was evaporated in vacuo
  6. customto give the crude product
  7. customThe crude product was purified by preparative TLC on silica gel (0.50 mm thickness)
  8. washeluting with 30% EtOAc/Hexane

Sources & evidence

ORD record
ord-c0724da93fde49bd917e86752a50f0d0
Source dataset
uspto-grants-2013_12
Patent number
US08598161B2

Reaction notes

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