Sodium Hydroxide → rel-(4aS,11bS)-10-bromo-11b-methyl-4a,5,6,11b-tetrahydro-4H-benzo[2,3]oxepino[4,5-d][1,3]thiazin-2-amine

HRID 1911023Notes

Reaction equation

HRID 1911023 reaction equation
Cl.[C:2]([S:5][CH2:6][C:7]1[CH2:13][CH2:12][O:11][C:10]2[CH:14]=[CH:15][C:16]([Br:18])=[CH:17][C:9]=2[C:8]=1[CH3:19])(=[NH:4])[NH2:3].OS(C(F)(F)F)(=O)=O.[OH-].[Na+].C([O-])(O)=O.[Na+]>C(O)(C(F)(F)F)=O.C(OCC)C>[Br:18][C:16]1[CH:15]=[CH:14][C:10]2[O:11][CH2:12][CH2:13][C@@H:7]3[CH2:6][S:5][C:2]([NH2:3])=[N:4][C@:8]3([CH3:19])[C:9]=2[CH:17]=1

Participants

7

Reactant 4

HCID 14798Sodium HydroxideHCID 62406Trifluoromethanesulfonic acidHCID 516892Sodium BicarbonateHCID 86685423(7-Bromo-5-methyl-2,3-dihydrobenzo[b]oxepin-4-yl)methyl carbamimidothioate hydrochloride

Product 1

HCID 86685425rel-(4aS,11bS)-10-bromo-11b-methyl-4a,5,6,11b-tetrahydro-4H-benzo[2,3]oxepino[4,5-d][1,3]thiazin-2-amineYield 56%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6422Trifluoroacetic acidSolvent

Procedure

To a solution of (7-bromo-5-methyl-2,3-dihydrobenzo[b]oxepin-4-yl)methyl carbamimidothioate hydrochloride from step H8 (2.59 g, 7.12 mmol) in TFA (20 mL) was added triflic acid (5.0 mL). The mixture was stirred at rt for 3 h. The reaction mixture was chilled to 0° C. then diluted with diethyl ether (150 mL). The resulting mixture was slowly neutralized with 50% aqueous NaOH and made basic (pH=12) with saturated aqueous NaHCO3 solution. The organic layer was separated, dried over sodium sulfate, filtered, and concentrated in vacuo. The crude material was purified by silica gel column chromography (30-100% EtOAc/hexanes) to afford rel-(4aS,11bS)-10-bromo-11b-methyl-4a,5,6,11b-tetrahydro-4H-benzo[2,3]oxepino[4,5-d][1,3]thiazin-2-amine (1.31 g, 4.00 mmol, 56% yield). LCMS (M+H)+=329.0. 1H NMR (500 MHz, methanol-d4) δ 7.50 (dd, J=8.5, 2.4 Hz, 1H), 7.18 (d, J=2.4 Hz, 1H), 7.05 (d, J=8.4 Hz, 1H), 4.38-4.31 (m, 1H), 3.76 (td, J=13.2, 1.5 Hz, 1H), 3.05-2.92 (m, 2H), 2.85 (ddt, J=15.5, 13.4, 4.5 Hz, 1H), 2.55-2.47 (m, 1H), 1.96-1.88 (m, 1H), 1.86 (s, 3H).

Workup

  1. temperatureThe reaction mixture was chilled to 0° C.
  2. customThe organic layer was separated
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude material was purified by silica gel column chromography (30-100% EtOAc/hexanes)

Sources & evidence

ORD record
ord-ce4d2a2a462846dcb2b9c0fd3ff7065a
Source dataset
uspto-grants-2013_12
Patent number
US08604024B2

Reaction notes

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