tert-Butyl ((4aS,5S,7aS)-7a-(2-fluoro-5-nitrophenyl)-5-(trifluoromethyl)-4a,5,7,7a-tetrahydro-4H-furo[3,4-d][1,3]thiazin-2-yl)carbamate → tert-butyl[(4aS,5S,7aS)-7a-(5-amino-2-fluorophenyl)-5-trifluoromethyl-4a,5,7,7a-tetrahydro-4H-furo[3,4-d][1,3]thiazin-2-yl]carbamate

HRID 2045846Notes

Reaction equation

HRID 2045846 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-])=O)=[CH:4][C:3]=1[C@:11]12[CH2:19][O:18][C@H:17]([C:20]([F:23])([F:22])[F:21])[C@H:16]1[CH2:15][S:14][C:13]([NH:24][C:25](=[O:31])[O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[N:12]2.O.O.[Sn](Cl)(Cl)(Cl)Cl>C(O)C>[NH2:8][C:5]1[CH:6]=[CH:7][C:2]([F:1])=[C:3]([C@:11]23[CH2:19][O:18][C@H:17]([C:20]([F:23])([F:21])[F:22])[C@H:16]2[CH2:15][S:14][C:13]([NH:24][C:25](=[O:31])[O:26][C:27]([CH3:28])([CH3:30])[CH3:29])=[N:12]3)[CH:4]=1

Participants

4

Reactant 2

HCID 68171523tert-Butyl ((4aS,5S,7aS)-7a-(2-fluoro-5-nitrophenyl)-5-(trifluoromethyl)-4a,5,7,7a-tetrahydro-4H-furo[3,4-d][1,3]thiazin-2-yl)carbamateHCID 85782573Tin tetrachloride dihydrate

Product 1

HCID 68171522tert-butyl[(4aS,5S,7aS)-7a-(5-amino-2-fluorophenyl)-5-trifluoromethyl-4a,5,7,7a-tetrahydro-4H-furo[3,4-d][1,3]thiazin-2-yl]carbamateYield 99.9%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

tert-Butyl ((4aS,5S,7aS)-7a-(2-fluoro-5-nitrophenyl)-5-(trifluoromethyl)-4a,5,7,7a-tetrahydro-4H-furo[3,4-d][1,3]thiazin-2-yl)carbamate (16.61 g) was dissolved in ethanol (250 mL) and tin chloride dihydrate (25.0 g) was added. After stirring at RT for 18 h, the solution was poured onto NaOH (2N aq., 300 mL) and Celite® (˜50 g) was added. The resulting mixture was filtered through more Celite® and extracted with EtOAc (2×500 mL). The combined organic portions were dried over MgSO4 and evaporated to afford the title compound (15.52 g). This material could be used crude but a portion was purified by silica gel column chromatography (20% to 50% EtOAc in hexanes) to afford pure material (recovery 79%). 1H NMR (400 MHz, CDCl3) δ ppm 1.53 (s, 9H), 2.77 (d, J=14.4 Hz, 1H), 3.09 (br. s., 1H), 3.46 (br. s., 1H), 3.62 (br. s., 2H), 3.87 (br. s., 1H), 4.61 (d, J=8.6 Hz, 1H), 4.71 (br. s., 1H), 6.61 (br. s., 2H), 6.85-6.95 (m, 1H)

Workup

  1. additionthe solution was poured onto NaOH (2N aq., 300 mL) and Celite® (˜50 g)
  2. additionwas added
  3. filtrationThe resulting mixture was filtered through more Celite®
  4. extractionextracted with EtOAc (2×500 mL)
  5. dry with materialThe combined organic portions were dried over MgSO4
  6. customevaporated

Sources & evidence

ORD record
ord-58ab187be9fc4f1ba9c8e59b428f3431
Source dataset
uspto-grants-2013_11
Patent number
US08592408B2

Reaction notes

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