Toluene → HCID 86700136, compound

HRID 879337Notes

Reaction equation

HRID 879337 reaction equation
[Br:1][C:2]1[S:3][C:4]2[C:10](=[O:11])[CH2:9][CH:8]([CH3:12])[CH2:7][C:5]=2[N:6]=1.C([C:15](=O)[C:16]([O-:18])=[O:17])C.[C:20]1(C)C=CC=C[CH:21]=1.CC(C)([O-])C.[Li+]>C1COCC1>[Br:1][C:2]1[S:3][C:4]2[C:10](=[O:11])/[C:9](=[CH:15]/[C:16]([O:18][CH2:20][CH3:21])=[O:17])/[CH:8]([CH3:12])[CH2:7][C:5]=2[N:6]=1

Participants

6

Reactant 4

HCID 1140TolueneHCID 35932772-KetobutyrateHCID 236647642-Propanol, 2-methyl-, lithium salt (1:1)HCID 70982538HCID 70982538, compound

Product 1

HCID 86700136HCID 86700136, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A 3.0 L round-bottom flask was charged with 2-bromo-5-methyl-5,6-dihydrobenzo[d]thiazol-7(4H)-one (75.0 g, 305 mmol, 1.00 equiv), anhydrous THF (750 mL), and a 50% w/v solution of ethylglyoxylate in toluene (211 mL, 1.07 mol, 3.50 equiv). The resulting solution was placed in a water bath. Solid lithium tert-butoxide (48.9 g, 610 mmol, 2.0 equiv) was steadily added over a 1 min period. The reaction was capped and stirred for 4.5 h. TLC (20% EtOAc/80% hexane indicated full consumption of 2-bromo-5-methyl-5,6-dihydrobenzo[d]thiazol-7(4H)-one). Saturated aqueous NH4Cl (750 mL) was added quickly. The reaction was stirred for 15 min. H2O (250 mL) was added. Most of the solids dissolved. 1.0 M aqueous HCl (180 mL) was added over a 5 min period. After a short time the pH of the aqueous layer was ˜3.5. The organic phase was collected, and the aqueous layer was extracted with EtOAc (2×375 mL). Combined organic layers were washed with brine (500 mL), dried (MgSO4), filtered, and concentrated to a minimum volume with a bath temperature of 50-60° C. and 10 mmHg vacuum. DCM (40 mL) was added. The resulting solution was transferred to a Combiflash XL solid loading cartridge by gravity loading. The solid cartridge was assembled in line with a 1.5 kg Combiflash XL silica gel column equilibrated with hexane. The following gradient elution sequence was used: [100% Hexane (5 column volumes, isocratic)→10% EtOAc/90% Hexane (10 column volumes, linear gradient)→10% EtOAc/90% Hexane (7 column volumes, isocratic))→100% EtOAc (8 column volumes, isocratic)]. Fractions containing product were combined, concentrated, and dried under high vacuum to give desired product. LCMS-ESI+ calc'd for C12H12BrNO3S: 330.0 and 332.0 (M+H+); found: 330.0 and 332.0 (M+H+). 1H NMR (400 MHz, CDCl3): δ 6.77 (s, 1H), 4.60-4.53 (m, 1H), 4.30-4.21 (m, 2H), 3.23 (dd, J=17.6, 5.8 Hz, 1H), 3.07 (d, J=5.8 Hz, 1H), 1.33 (t, J=7.2 Hz, 3H), 1.23 (d, J=7.0 Hz, 3H).

Workup

  1. customThe resulting solution was placed in a water bath
  2. customThe reaction was capped
  3. customTLC (20% EtOAc/80% hexane indicated full consumption of 2-bromo-5-methyl-5,6-dihydrobenzo[d]thiazol-7(4H)-one)
  4. additionSaturated aqueous NH4Cl (750 mL) was added quickly
  5. stirringThe reaction was stirred for 15 min
  6. additionH2O (250 mL) was added
  7. dissolutionMost of the solids dissolved
  8. addition1.0 M aqueous HCl (180 mL) was added over a 5 min period
  9. customThe organic phase was collected
  10. extractionthe aqueous layer was extracted with EtOAc (2×375 mL)
  11. washCombined organic layers were washed with brine (500 mL)
  12. dry with materialdried (MgSO4)
  13. filtrationfiltered
  14. concentrationconcentrated to a minimum volume with a bath temperature of 50-60° C. and 10 mmHg vacuum
  15. additionDCM (40 mL) was added
  16. washThe following gradient elution sequence
  17. additionFractions containing product
  18. concentrationconcentrated
  19. customdried under high vacuum

Sources & evidence

ORD record
ord-a1e732d76d5944f48afc495b07aaa885
Source dataset
uspto-grants-2015_03
Patent number
US08987250B2

Reaction notes

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