Trifluoromethanesulfonic acid → Trifluoroacetic acid

HRID 1911009Notes

Reaction equation

HRID 1911009 reaction equation
OS([C:5]([F:8])([F:7])[F:6])(=O)=O.Cl.[C:10]([S:13][CH2:14][C:15]1[CH2:16][CH2:17][CH2:18][C:19]2[CH:26]=[CH:25][C:24]([Br:27])=[CH:23][C:20]=2[C:21]=1[CH3:22])(=[NH:12])[NH2:11].[C:28](=O)([OH:30])[O-:29].[Na+]>C(O)(C(F)(F)F)=O>[Br:27][C:24]1[CH:25]=[CH:26][C:19]2[CH2:18][CH2:17][CH2:16][C@@H:15]3[CH2:14][S:13][C:10]([NH2:11])=[N:12][C@:21]3([CH3:22])[C:20]=2[CH:23]=1.[C:28]([OH:30])([C:5]([F:8])([F:7])[F:6])=[O:29]

Participants

6

Reactant 3

HCID 62406Trifluoromethanesulfonic acidHCID 516892Sodium BicarbonateHCID 131731075HCID 131731075, compound

Product 2

HCID 6422Trifluoroacetic acidYield 12%HCID 71084848HCID 71084848, compound

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Procedure

Triflic acid (1.33 mL, 15.0 mmol) was added to flask charged with a stirred solution of (2-bromo-9-methyl-6,7-dihydro-5H-benzo[7]annulen-8-yl)methyl carbamimidothioate, HCl from step E3 (540 mg, 1.5 mmol) in TFA (5.0 mL) at 0° C. The reaction mixture was allowed to warm to rt and stir for 6 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 ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated in vacuo. The crude product was purified using preparatory HPLC (SunFire PrepC18 OBD 10 mm, 50×250 mm column, 90% MeOH/10% water/0.1% TFA-90% MeOH/10% water/0.1% TFA, linear gradiant over 34 min, 50 ml/min) to afford (4aS,11bS)-10-bromo-11b-methyl-4,4a,5,6,7,11b-hexahydrobenzo[6,7]cyclohepta[1,2-d][1,3]thiazin-2-amine, TFA (77 mg, 0.18 mmol, 12% yield) as a white solid. LCMS (M+H)+=327.0. 1H NMR (500 MHz, methanol-d4) δ 7.43 (dd, J=8.1, 2.1 Hz, 1H), 7.26 (d, J=2.1 Hz, 1H), 7.20 (d, J=8.1 Hz, 1H), 3.17-3.06 (m, 1H), 2.96 (dd, J=12.1, 3.1 Hz, 1H), 2.89 (dd, J=15.4, 5.6 Hz, 1H), 2.80 (t, J=12.4 Hz, 1H), 2.57-2.39 (m, 2H), 2.08 (dd, J=14.8, 4.0 Hz, 1H), 1.94-1.86 (m, 1H), 1.84 (s, 3H), 1.67-1.48 (m, 1H).

Workup

  1. customThe reaction contents
  2. extractionthe resulting mixture was extracted with ethyl acetate
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude product was purified
  8. customHPLC (SunFire PrepC18 OBD 10 mm, 50×250 mm column, 90% MeOH/10% water/0.1% TFA-90% MeOH/10% water/0.1% TFA, linear gradiant over 34 min, 50 ml/min)

Sources & evidence

ORD record
ord-ad33ff532ff94a049c67370314132bc1
Source dataset
uspto-grants-2013_12
Patent number
US08604024B2

Reaction notes

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