Sodium Bicarbonate → HCID 86762146, compound

HRID 1907408Notes

Reaction equation

HRID 1907408 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]([F:18])=[C:6]([C@:8]23[O:16][CH2:15][CH2:14][C@H:13]2[CH2:12][S:11][C:10]([NH2:17])=[N:9]3)[CH:7]=1.[C:19](=[O:22])(O)[O-:20].[Na+]>O1CCOCC1.O>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([F:18])=[C:6]([C@:8]23[O:16][CH2:15][CH2:14][C@H:13]2[CH2:12][S:11][C:10]([NH:17][C:19](=[O:22])[O:20][C:6]([CH3:8])([CH3:7])[CH3:5])=[N:9]3)[CH:7]=1

Participants

5

Reactant 2

HCID 516892Sodium BicarbonateHCID 71060839HCID 71060839, compound

Product 1

HCID 86762146HCID 86762146, compoundYield 56%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 312751,4-DioxaneSolvent

Procedure

To a solution of (4aR,7aR)-7a-(5-bromo-2-fluorophenyl)-4a,5,6,7a-tetrahydro-4H-furo[2,3-d][1,3]thiazin-2-amine (4.8 g, 14.5015 mmol) in 1,4-Dioxane (40 mL) was added di-tert-butyl bicarbonate (6.19 mL, 29.003 mmol) followed by addition of saturated sodium bicarbonate (33.6 mL) and water (4.8 mL) at rt, and the reaction mixture was stirred at rt for 12 h. The reaction mixture was diluted with water (150 mL) and extracted with ethyl acetate (3×100 mL), and the combined organics were dried over the sodium sulphate and concentrated under reduced pressure to give the crude product. The crude product was purified by silica gel column chromatography eluting with 30-40% ethyl acetate-hexanes (combiflash) to give the title compound as a white solid (3.5 g, 56% yield). 1H NMR (400 MHz, CDCl3) δ 7.67 (1H, dd, J=2.4, 6.8 Hz), 7.43 (1H, dt, J=1.2, 6.8 Hz), 6.96 (1H, dd, J=8.4, 11.2 Hz), 4.13 (1H, m), 4.03 (1H, m), 3.26 (1H, m), 2.86 (2H, m), 2.36 (1H, m), 2.21 (1H, m), and 1.47 (9H, s). MS (M+H)+:431.0, 435.0

Workup

  1. extractionextracted with ethyl acetate (3×100 mL)
  2. dry with materialthe combined organics were dried over the sodium sulphate
  3. concentrationconcentrated under reduced pressure
  4. customto give the crude product
  5. customThe crude product was purified by silica gel column chromatography
  6. washeluting with 30-40% ethyl acetate-hexanes (combiflash)

Sources & evidence

ORD record
ord-b72952f81d9e445fa12c70377a82925c
Source dataset
uspto-grants-2013_12
Patent number
US08598161B2

Reaction notes

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