Trifluoroacetic acid → (4aR,11bR)-3,3,11b-trimethyl-4,4-dioxo-5,6-dihydro-4aH-[1]benzoxepino[4,5-b][1,4]thiazine-2,10-diamine

HRID 627626Notes

Reaction equation

HRID 627626 reaction equation
[NH2:1][C:2]1[CH:3]=[CH:4][C:5]2[O:27][CH2:26][CH2:25][C@H:8]3[S:9](=[O:24])(=[O:23])[C:10]([CH3:22])([CH3:21])[C:11]([NH:13]C(=O)OC(C)(C)C)=[N:12][C@:7]3([CH3:28])[C:6]=2[CH:29]=1.FC(F)(F)C(O)=O>C(Cl)Cl>[CH3:21][C:10]1([CH3:22])[S:9](=[O:23])(=[O:24])[C@@H:8]2[CH2:25][CH2:26][O:27][C:5]3[CH:4]=[CH:3][C:2]([NH2:1])=[CH:29][C:6]=3[C@@:7]2([CH3:28])[N:12]=[C:11]1[NH2:13]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 90307362tert-butyl ((4aR,11bR)-10-amino-3,3,11b-trimethyl-4,4-dioxido-4a,5,6,11b-tetrahydro-3H-benzo[6,7]oxepino[4,5-b][1,4]thiazin-2-yl)carbamate2×

Product 1

HCID 90307372(4aR,11bR)-3,3,11b-trimethyl-4,4-dioxo-5,6-dihydro-4aH-[1]benzoxepino[4,5-b][1,4]thiazine-2,10-diamineYield 77%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of tert-butyl ((4aR,11bR)-10-amino-3,3,11b-trimethyl-4,4-dioxido-4a,5,6,11b-tetrahydro-3H-benzo[6,7]oxepino[4,5-b][1,4]thiazin-2-yl)carbamate (intermediate 19) (308 mg, 0.727 mmol) in DCM (5.5 ml) was treated with trifluoroacetic acid (2.70 ml, 36.4 mmol) for 15 min. The mixture was concentrated, redissolved in DCM, diluted with water and free-based with a saturated solution of NaHCO3. The mixture was extracted with DCM, organic extract was washed with brine, filtered through pad of celite and concentrated to afford (4aR,11bR)-3,3,11b-trimethyl-4,4-dioxo-5,6-dihydro-4aH-[1]benzoxepino[4,5-b][1,4]thiazine-2,10-diamine (180 mg, 0.557 mmol, 77% yield) as an off-white solid. LC/MS (ESI+) m/z=324.2 (M+H).

Workup

  1. concentrationThe mixture was concentrated
  2. dissolutionredissolved in DCM
  3. additiondiluted with water and free-based with a saturated solution of NaHCO3
  4. extractionThe mixture was extracted with DCM
  5. extractionorganic extract
  6. washwas washed with brine
  7. filtrationfiltered through pad of celite
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-0beb2f907b364f8f8daa29b052a47418
Source dataset
uspto-grants-2016_04
Patent number
US09309263B2

Reaction notes

Loading…