Sodium Bicarbonate → (S)-ethyl 2-(2-bromo-7-(4-chlorophenyl)-5-methylbenzo[d]thiazol-6-yl)-2-tert-butoxyacetate

HRID 879341Notes

Reaction equation

HRID 879341 reaction equation
[Br:1][C:2]1[S:3][C:4]2[C:10]([C:11]3[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][CH:12]=3)=[C:9]([C@H:18]([OH:24])[C:19]([O:21][CH2:22][CH3:23])=[O:20])[C:8]([CH3:25])=[CH:7][C:5]=2[N:6]=1.C([O-])(O)=O.[Na+]>C(OC(C)=O)(C)(C)C>[Br:1][C:2]1[S:3][C:4]2[C:10]([C:11]3[CH:12]=[CH:13][C:14]([Cl:17])=[CH:15][CH:16]=3)=[C:9]([C@H:18]([O:24][C:8]([CH3:25])([CH3:9])[CH3:7])[C:19]([O:21][CH2:22][CH3:23])=[O:20])[C:8]([CH3:25])=[CH:7][C:5]=2[N:6]=1

Participants

4

Reactant 2

HCID 516892Sodium BicarbonateHCID 86700139(S)-ethyl 2-(2-bromo-7-(4-chlorophenyl)-5-methylbenzo[d]thiazol-6-yl)-2-hydroxyacetate

Product 1

HCID 86700141(S)-ethyl 2-(2-bromo-7-(4-chlorophenyl)-5-methylbenzo[d]thiazol-6-yl)-2-tert-butoxyacetate

Reagents, catalysts & solvents 1

HCID 10908tert-Butyl acetateSolvent

Conditions

Temperature
0 °C

Procedure

A suspension of (S)-ethyl 2-(2-bromo-7-(4-chlorophenyl)-5-methylbenzo[d]thiazol-6-yl)-2-hydroxyacetate (7.20 g, 16.9 mmol) in neat t-BuOAc (100 mL) was cooled to 0° C. in an ice bath. 70% w/v aqueous HClO4 (293 μL, 3.4 mmol) was added dropwise over 5 min. The reaction was warmed to 23° C., then stirred for 2.3 h. At this point the reaction was transferred to an addition funnel. The reaction was added to a 23° C. solution of sat aqueous NaHCO3 (400 mL) over 30 min. Once addition was complete, the reaction was stirred for another 15 min. The resulting system was extracted with EtOAc (2×150 mL). Combined organic layers were dried (Na2SO4), filtered, and concentrated in vacuo. Some residual t-BuOAc remained. Hexane (200 mL) was added and the slurry was concentrated once more. The resulting residue (reasonably free of t-BuOAc) was treated with Benzene and loaded onto a 330 g “gold” ISCO silica gel column. The following gradient elution sequence was used: [100% Hexane (5 column volumes, isocratic)→10% EtOAc/90% Hexane (5 column volumes, linear gradient→10% EtOAc/90% Hexane (5 column volumes, isocratic ((S)-ethyl 2-(2-bromo-7-(4-chlorophenyl)-5-methylbenzo[d]thiazol-6-yl)-2-tert-butoxyacetate elutes))→100% EtOAc (10 column volumes, isocratic, (unreacted (S)-ethyl 2-(2-bromo-7-(4-chlorophenyl)-5-methylbenzo[d]thiazol-6-yl)-2-hydroxyacetate elutes))]. Product-containing fractions were pooled, concentrated, co-evarporated with Et2O (100 mL) to give desired product. LCMS-ESI+ calc'd for C22H23BrClNO3S: 496.0, 498.0 and 500.0 (M+H+); found: 496.2, 498.2, and 500.1 (M+H+). 1H NMR (400 MHz, CDCl3): δ 7.77 (s, 1H), 7.48 (m, 3H), 7.37 (m, 1H), 5.12 (s, 1H), 4.20 (m, 2H), 2.57 (s, 3H), 1.24 (t, 3H, J=7 Hz), 0.96 (s, 9H).

Workup

  1. additionwas added dropwise over 5 min
  2. temperatureThe reaction was warmed to 23° C.
  3. customAt this point the reaction was transferred to an addition funnel
  4. additionOnce addition
  5. stirringthe reaction was stirred for another 15 min
  6. extractionThe resulting system was extracted with EtOAc (2×150 mL)
  7. dry with materialCombined organic layers were dried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. additionHexane (200 mL) was added
  11. concentrationthe slurry was concentrated once more
  12. additionThe resulting residue (reasonably free of t-BuOAc) was treated with Benzene
  13. washThe following gradient elution sequence
  14. concentrationconcentrated, co-evarporated with Et2O (100 mL)

Sources & evidence

ORD record
ord-53c1d0e298a840b982d0588598a5a02d
Source dataset
uspto-grants-2015_03
Patent number
US08987250B2

Reaction notes

Loading…