Acetic Acid → 6H-thiazolo[5,4-e]indol-7(8H)-one

HRID 2297860Notes

Reaction equation

HRID 2297860 reaction equation
CS[CH:3]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]3[N:14]=[CH:13][S:12][C:10]3=2)[NH:5][C:4]1=[O:15].C(O)(=O)C>C1COCC1.[Zn]>[S:12]1[C:10]2=[C:11]3[C:6](=[CH:7][CH:8]=[C:9]2[N:14]=[CH:13]1)[NH:5][C:4](=[O:15])[CH2:3]3

Participants

5

Reactant 2

HCID 176Acetic AcidHCID 110536548-methylsulfanyl-6,8-dihydro-1-thia-3,6-diaza-as-indacen-7-one

Product 1

HCID 111168276H-thiazolo[5,4-e]indol-7(8H)-oneYield 70%

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

A 2-L three-neck round bottom flask was fitted with an internal thermometer, 250-mL addition funnel, magnetic stir bar and septa. The flask was charged with nitrogen, 200 mL of dry THF, and 6-aminobenzothiazole (15.2 g, 0.100 mol). The mixture was stirred and cooled in a dry ice-acetone bath to an internal temperature of −74° C. A solution of tert-butyl hypochlorite (11.0 g, 0.103 mol) in 50 mL of dichloromethane was added over a 15 minute period. The resultant solution was stirred for an additional 3 hours at dry ice-acetone bath temperature. To the reaction was then added by slow, dropwise addition a solution of ethyl methylthioacetate (13.8 g, 0.103 mol) in 50 mL of dichoromethane. The resultant solution was stirred for an additional 3 hours at dry ice-acetone bath temperature. A solution of triethyl amine (25.3 g, 0.250 mol) and 50 ml of dichloromethane was added at dry ice-acetone bath temperature, and the solution was stirred for 0.5 hours. The cooling bath was removed, and the reaction was allowed to warm to room temperature. The reaction was then concentrated to a thick residue. The thick oil was resuspended in 200 mL of ether and 600 mL of 0.25 M hydrochloric acid. The mixture was allowed to stir for 24 h. The resulting solid was filtered from the mixture and triturated with water and ether. The solid was then resuspended in cold MeOH, filtered and dried under vacum for 16 hours to yield 18.7 g (79%) of 8-(methylsulfanyl)-6,8-dihydro-7H-[1,3]thiazolo[5,4-e]indol-7-one: 1H NMR (DMSO-d6)δ 10.8 (s, 1H), 9.2 (s, 1H), 8.0 (d, 1H), 7.1 (d, 1H), 1.8 (s, 3H); APCI-MS m/z 235 (M-H). To a 500-mL Erlenmeyer flask was added a stir bar, 8.1 g (0.034 moles) of 8-(methylsulfanyl)-6,8-dihydro-7H-[1,3]thiazolo[5,4-e]indol-7-one and 100 mL of glacial acetic acid. The mixture was stirred until all the starting material had dissolved. The reaction mixture was then diluted with 100 mL of THF. Zinc metal (16 g, 325 mesh) was then added. The heterogeneous mixture was then stirred and heated to 60° C. for 2.5 hours. The mixture was vacuum filtered through a one half-inch pad of celite. The residue on the filter pad was washed with additional THF. The filtrates were combined and concentrated to a wet solid. The solid was triturated with MeOH, filtered and air dried to yield 4.51 g (70%) of the compound as a free-flowing solid: 1H NMR (DMSO-d6): δ 10.5 (s, 1H), 9.1 (s, 1H), 7.9 (d,;1H), 7.0 (d, 1H), 3.6 (s, 2H); APCI-MS m/z 191 (M+H)+.

Workup

  1. additionTo a 500-mL Erlenmeyer flask was added a stir bar
  2. dissolutionhad dissolved
  3. stirringThe heterogeneous mixture was then stirred
  4. filtrationfiltered through a one half-inch pad of celite
  5. washThe residue on the filter pad was washed with additional THF
  6. concentrationconcentrated to a wet solid
  7. customThe solid was triturated with MeOH
  8. filtrationfiltered
  9. customair dried

Sources & evidence

ORD record
ord-6b8e4c4256ac47f2b953ac69abd115d8
Source dataset
uspto-grants-2002_12
Patent number
US06492398B1

Reaction notes

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