Trifluoromethanesulfonic acid → HCID 86685418, compound

HRID 1911006Notes

Reaction equation

HRID 1911006 reaction equation
OS(C(F)(F)F)(=O)=O.[C:9]([S:12][CH2:13][C:14]1[CH2:23][CH2:22][C:21]2[C:16](=[CH:17][C:18]([Br:24])=[CH:19][CH:20]=2)[C:15]=1[CH3:25])(=[NH:11])[NH2:10].C(=O)(O)[O-].[Na+]>C(O)(C(F)(F)F)=O>[Br:24][C:18]1[CH:17]=[C:16]2[C:21]([CH2:22][CH2:23][C@@H:14]3[CH2:13][S:12][C:9]([NH2:10])=[N:11][C@:15]32[CH3:25])=[CH:20][CH:19]=1

Participants

5

Reactant 3

HCID 62406Trifluoromethanesulfonic acidHCID 516892Sodium BicarbonateHCID 86685417HCID 86685417, compound

Product 1

HCID 86685418HCID 86685418, compound

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Conditions

Temperature
0 °C

Procedure

Triflic acid (0.25 mL, 2.82 mmol) was added to flask charged with a stirred solution of (7-bromo-1-methyl-3,4-dihydronaphthalen-2-yl)methyl carbamimidothioate from step C3 (255 mg, 0.819 mmol) in TFA (2.5 mL) at 0° C. The resulting mixture was capped and left to stir at 0° C. for 2 h. The reaction contents were carefully added to a swirled mixture of ice and excess solid sodium bicarbonate. After gas evolution had ceased, the resulting mixture was extracted with EtOAc. The combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated in vacuo to afford rel-(4aS,10bR)-9-bromo-10b-methyl-4a,5,6,10b-tetrahydro-4H-naphtho[1,2-d][1,3]thiazin-2-amine as a white solid. The crude product was dissolved in THF (2.5 mL). Triethylamine (0.457 mL, 3.28 mmol), di-tert-butyl dicarbonate (0.571 mL, 2.458 mmol), and DMAP (5.00 mg, 0.041 mmol) were added to the crude product. After 16 h, the reaction mixture was concentrated in vacuo and purified using silica gel column chromatography (10:1 hexanes/EtOAc) to afford tert-butyl rel-((4aS,10bS)-9-bromo-10b-methyl-4a,5,6,10b-tetrahydro-4H-naphtho[1,2-d][1,3]thiazin-2-yl)carbamate (244 mg, 0.581 mmol, 71.0% yield) as a white solid. LCMS (M+H)+=225.0. 1H NMR (500 MHz, chloroform-d) δ 7.61 (br. s., 1H), 7.32 (dd, J=8.2, 1.8 Hz, 1H), 6.98 (d, J=8.2 Hz, 1H), 3.04 (dd, J=12.9, 3.6 Hz, 1H), 2.88 (dd, J=13.0, 8.2 Hz, 1H), 2.83 (t, J=6.9 Hz, 2H), 2.36-2.20 (m, 1H), 2.19-2.08 (m, 1H), 2.04-1.95 (m, 1H), 1.62 (s, 3H), 1.49 (s, 9H).

Workup

  1. customThe resulting mixture was capped
  2. waitleft
  3. customThe reaction contents
  4. extractionthe resulting mixture was extracted with EtOAc
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-554fc24e8d0049b5aaa7dee0c0983716
Source dataset
uspto-grants-2013_12
Patent number
US08604024B2

Reaction notes

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