Ammonium Chloride → HCID 88920474, compound

HRID 529404Notes

Reaction equation

HRID 529404 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:14](=[CH:15][CH:16]=1)[O:13][C:7]1[CH:8]=[N:9][C:10]([Cl:12])=[CH:11][C:6]=1/[C:5]/2=[N:17]\[S@:18]([C:20]([CH3:23])([CH3:22])[CH3:21])=[O:19].[Cl-].[C:25]([O:29][C:30](=[O:33])[CH2:31][Zn+])([CH3:28])([CH3:27])[CH3:26].[NH4+].[Cl-]>C1COCC1>[Br:1][C:2]1[CH:3]=[C:4]2[C:14](=[CH:15][CH:16]=1)[O:13][C:7]1[CH:8]=[N:9][C:10]([Cl:12])=[CH:11][C:6]=1[C@@:5]2([CH2:31][C:30]([O:29][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:33])[NH:17][S@:18]([C:20]([CH3:23])([CH3:22])[CH3:21])=[O:19].[Br:1][C:2]1[CH:3]=[C:4]2[C:14](=[CH:15][CH:16]=1)[O:13][C:7]1[CH:8]=[N:9][C:10]([Cl:12])=[CH:11][C:6]=1[C@:5]2([CH2:31][C:30]([O:29][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:33])[NH:17][S@:18]([C:20]([CH3:23])([CH3:22])[CH3:21])=[O:19]

Participants

6

Reactant 3

HCID 25517Ammonium ChlorideHCID 88949056HCID 88949056, compoundHCID 178451183HCID 178451183, compound

Product 2

HCID 88920474HCID 88920474, compoundHCID 89943867HCID 89943867, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of (S,Z)-N-(7-bromo-3-chloro-5H-chromeno[2,3-c]pyridin-5-ylidene)-2-methylpropane-2-sulfinamide (3000 mg, 7.25 mmol) in THF (25 mL) was slowly added 2-tert-butoxy-2-oxoethylzinc chloride (0.5 M in diethyl ether, 36.3 mL, 18.13 mmol) in an ice bath. The mixture was stirred at 0° C. for 25 mins, then 80 mL of saturated NH4Cl aqueous solution was added to quench the reaction. The reaction mixture was extracted with EtOAc (2×35 mL). The organic extract was washed with saturated NaCl aqueous solution, dried over MgSO4, filtered and concentrated to give the crude material as an orange solid. The crude material was absorbed onto a plug of silica gel and purified by chromatography through a Redi-Sep pre-packed silica gel column (80 g), eluting with a gradient of 0% to 20% to 50% DCM/MeOH (90/10) in DCM. The fractions which contain mixture were repurified using 40 g Redi-Sep pre-packed silica gel column and eluting with a gradient of 0% to 20% to 50% DCM/MeOH (90/10) in DCM. The desired fractions were collected and concentrated to provide tert-butyl 2-((S)-7-bromo-3-chloro-5-((S)-1,1-dimethylethylsulfinamido)-5H-chromeno[2,3-c]pyridin-5-yl)acetate (isomer A, high Rf), and tert-butyl 2-((R)-7-bromo-3-chloro-5-((S)-1,1-dimethylethylsulfinamido)-5H-chromeno[2,3-c]pyridin-5-yl)acetate (isomer B, low Rf) as off-white solid. Isomer A: 1H NMR (400 MHz, DMSO-d6) δ ppm 0.97 (s, 9 H) 1.03 (s, 9 H) 3.42 (s, 2 H) 6.41 (s, 1 H) 7.15 (d, J=8.71 Hz, 1 H) 7.52 (dd, J=8.80, 2.35 Hz, 1 H) 7.79 (s, 1 H) 7.98 (d, J=2.45 Hz, 1 H) 8.37 (s, 1 H). Isomer B: 1H NMR (400 MHz, DMSO-d6) δ ppm 0.97 (s, 9 H) 1.04 (s, 9 H) 3.34 (s, 1 H) 3.42 (s, 1 H) 6.35 (s, 1 H) 7.16 (d, J=8.80 Hz, 1 H) 7.54 (dd, J=8.80, 2.45 Hz, 1 H) 7.77 (d, J=2.35 Hz, 1 H) 7.95 (s, 1 H) 8.35 (s, 1 H).

Workup

  1. customto quench
  2. customthe reaction
  3. extractionThe reaction mixture was extracted with EtOAc (2×35 mL)
  4. extractionThe organic extract
  5. washwas washed with saturated NaCl aqueous solution
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto give the crude material as an orange solid
  10. customThe crude material was absorbed onto a plug of silica gel
  11. custompurified by chromatography through a Redi-Sep pre-packed silica gel column (80 g)
  12. washeluting with a gradient of 0% to 20% to 50% DCM/MeOH (90/10) in DCM
  13. customwere repurified
  14. washeluting with a gradient of 0% to 20% to 50% DCM/MeOH (90/10) in DCM
  15. customThe desired fractions were collected
  16. concentrationconcentrated

Sources & evidence

ORD record
ord-0d6ce03bd29a4c498a9fcda091b291b5
Source dataset
uspto-grants-2016_05
Patent number
US09346827B2

Reaction notes

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