Sodium Bicarbonate → (S)-tert-butyl(7'-bromo-4'-fluoro-2'-methoxy-5,6-dihydrospiro[[1,3]thiazine-4,9'-xanthen]-2-yl)carbamate

HRID 931633Notes

Reaction equation

HRID 931633 reaction equation
[Br:1][C:2]1[CH:15]=[C:14]2[C:5]([O:6][C:7]3[C:8]([F:24])=[CH:9][C:10]([O:22][CH3:23])=[CH:11][C:12]=3[C@@:13]32[CH2:20][CH2:19][S:18][C:17]([NH2:21])=[N:16]3)=[CH:4][CH:3]=1.[C:25](=[O:28])(O)[O-:26].[Na+]>O1CCOCC1.C(OCC)(=O)C>[C:12]([O:26][C:25](=[O:28])[NH:21][C:17]1[S:18][CH2:19][CH2:20][C@@:13]2([N:16]=1)[C:12]1[CH:11]=[C:10]([O:22][CH3:23])[CH:9]=[C:8]([F:24])[C:7]=1[O:6][C:5]1[C:14]2=[CH:15][C:2]([Br:1])=[CH:3][CH:4]=1)([CH3:13])([CH3:11])[CH3:7]

Participants

5

Reactant 2

HCID 516892Sodium BicarbonateHCID 89473220(S)-7'-bromo-4'-fluoro-2'-methoxy-5,6-dihydrospiro[[1,3]thiazine-4,9'-xanthen]-2-amine

Product 1

HCID 117624180(S)-tert-butyl(7'-bromo-4'-fluoro-2'-methoxy-5,6-dihydrospiro[[1,3]thiazine-4,9'-xanthen]-2-yl)carbamateYield 98%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

(S)-7′-bromo-4′-fluoro-2′-methoxy-5,6-dihydrospiro[[1,3]thiazine-4,9′-xanthen]-2-amine (400 mg, 0.977 mmol) was dissolved in dioxane (48870. Saturated aqueous sodium bicarbonate solution (5 mL) was added, followed by addition of Boc-anhydride (681 μl, 2.93 mmol). The reaction mixture was stirred at room temperature for 2 hrs. Then it was diluted with ethyl acetate and washed with water. The aqueous layer was extracted with ethyl acetate, and the combined organic layers were dried with MgSO4, filtered, and concentrated. The material was purified through column chromatography eluting with a gradient of 45% to 60% to 75% EtOAc in Hexane to afford (S)-tert-butyl(7′-bromo-4′-fluoro-2′-methoxy-5,6-dihydrospiro[[1,3]thiazine-4,9′-xanthen]-2-yl)carbamate (490 mg, 0.962 mmol, 98% yield) as a yellow solid.

Workup

  1. washwashed with water
  2. extractionThe aqueous layer was extracted with ethyl acetate
  3. dry with materialthe combined organic layers were dried with MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe material was purified through column chromatography
  7. washeluting with a gradient of 45% to 60% to 75% EtOAc in Hexane

Sources & evidence

ORD record
ord-98fcf0a7c55e4a688b7348e05fc671b8
Source dataset
uspto-grants-2016_03
Patent number
US09296759B2

Reaction notes

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