Bromine → HCID 89573799, compound

HRID 1911015Notes

Reaction equation

HRID 1911015 reaction equation
[Br:1]Br.[F:3][C:4]1[CH:5]=[CH:6][C:7]2[C@@:13]3([CH3:19])[N:14]=[C:15]([NH2:18])[S:16][CH2:17][C@H:12]3[CH2:11][O:10][C:8]=2[CH:9]=1.[OH-].[Na+].O.C(=O)(O)[O-].[Na+]>C(O)(=O)C>[Br:1][C:5]1[C:4]([F:3])=[CH:9][C:8]2[O:10][CH2:11][C@@H:12]3[CH2:17][S:16][C:15]([NH2:18])=[N:14][C@:13]3([CH3:19])[C:7]=2[CH:6]=1

Participants

6

Reactant 4

HCID 24408BromineHCID 516892Sodium BicarbonateHCID 23719242Sodium hydroxide--water (1/1/1)HCID 89573878HCID 89573878, compound

Product 1

HCID 89573799HCID 89573799, compoundYield 64%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

Bromine (0.20 mL, 3.80 mmol) was added dropwise to a solution of rel-(4aR,10bS)-8-fluoro-10b-methyl-4,4a,5,10b-tetrahydrochromeno[4,3-d][1,3]thiazin-2-amine from step F6 (644 mg, 2.55 mmol), in acetic acid (20 mL) at rt. The mixture was stirred for 30 min. The reaction was poured onto ice. The slurry was made pH 3 upon slow addition of 50% NaOH/water. The aqueous mixture was made basic pH 7-8 by the addition of solid sodium bicarbonate. The aqueous layers were extracted with EtOAc. The combined organic layers were dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was purified using silica gel column chromatography (0.25%-10% MeOH/CHCl3) to afford rel-(4aR,10bS)-9-bromo-8-fluoro-10b-methyl-4,4a,5,10b-tetrahydrochromeno[4,3-d][1,3]thiazin-2-amine (667 mg, 1.62 mmol, 64% yield) as a viscous oil. LCMS (M+H)+=333.02. 1H NMR (500 MHz, methanol-d4) δ 7.73 (d, J=7.5 Hz, 1H), 6.79 (d, J=9.8 Hz, 1H), 4.53 (dd, J=11.9, 2.9 Hz, 1H), 4.30 (dd, J=12.0, 6.0 Hz, 1H), 3.50 (dd, J=13.7, 3.9 Hz, 1H), 3.23 (dd, J=13.6, 8.1 Hz, 1H), 2.64 (dtd, J=10.0, 3.9, 3.0 Hz, 1H), 1.80 (s, 3H).

Workup

  1. additionThe reaction was poured onto ice
  2. extractionThe aqueous layers were extracted with EtOAc
  3. dry with materialThe combined organic layers were dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified

Sources & evidence

ORD record
ord-567419f536784dbe99d7feea8d3ce7e6
Source dataset
uspto-grants-2013_12
Patent number
US08604024B2

Reaction notes

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