Hydrochloric Acid → 1,2,3,4-Tetrahydro-benzo(b)azepin-5-one

HRID 1716259Notes

Reaction equation

HRID 1716259 reaction equation
[Li]CCCC.[S].Cl.S1C(SC[C:15]([N:17]2[C:26]3[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=3)[CH2:20][CH2:19][CH2:18]2)=O)=CC2C=CC=CC1=2.S1C(S)=CC2C=CC=CC1=2.[H-].[Na+].ClCC(N1C2C(=CC=CC=2)CCC1)=[O:46]>CCOCC.C1COCC1>[NH:17]1[CH2:15][CH2:18][CH2:19][C:20](=[O:46])[C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][C:26]1=2

Participants

10

Reactant 7

HCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 2401372-Chloro-1-(1,2,3,4-tetrahydroquinolin-1-yl)ethan-1-oneHCID 5362487SulfurHCID 11073791Benzo[b]thiophene-2-thiolHCID 59467886HCID 59467886, compoundHCID 178418339Butyllithium

Product 1

HCID 2947881,2,3,4-Tetrahydro-benzo(b)azepin-5-one

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

Compound 71 (1.75 g, 13.0 mmol) was dissolved in 40 mL of dry Et2O under N2 and the solution was cooled to 40° C. nBuLi (2.5 M solution in hexane, 5.7 mL, 14.3 mmol) was added and the reaction mixture was allowed to warm up to 0° C. during 1 h and then sulfur (0.414 g, 13.0 mmol) was added in one portion. The solution was allowed to slowly warm up to RT over 3 h. Excess of 10% HCl was added and the reaction mixture was stirred for 20 min. The thiol was extracted with ether, washed with brine, dried over Na2SO4 and concentrated to afford 2.0 g of crude compound 72 which was used in the next step without further purification. 2-(Benzo[b]thiophen-2-ylthio)-1-(3,4-dihydroquinolin-1(2H)-yl)ethanone (73): Crude compound 72 (0.71 g, 4.3 mmol) was dissolved in 40 mL of dry THF under N2, stirred for 30 min at RT and then cooled down to 0° C. NaH (60% in mineral oil, 0.224 g, 5.5 mmol) was added to the ice-cold solution which became a yellowish suspension. The formed suspension was stirred for 40 min at 0° C. and then 2-chloro-1-(3,4-dihydroquinolin-1(2H)-yl)ethanone (0.89 g, 4.3 mmol) was added as a solution in 4 mL of dry THF. The reaction mixture was stirred at RT for 16 h. The work-up, the same as for compound 5, gave crude material which was purified by flash chromatography (CH2Cl2/EtOAc) giving 0.56 g of the crude product. Pumping the crude product under high vacuum over P4O10 at 45° C. for 4 h removed the co-crystallized EtOAc to yield the desired product 73 (36%): MS: m/z+ 340.1 [M+H]+; Anal. Calcd (found) for C19H17NOS2: C, 67.22; (67.18), H, 5.05; (5.11), N, 4.13; (4.08), S, 18.89; (18.70).

Workup

  1. additionwas added
  2. temperatureto slowly warm up to RT over 3 h
  3. extractionThe thiol was extracted with ether
  4. washwashed with brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated
  7. customto afford 2.0 g of crude compound 72 which
  8. customwas used in the next step without further purification
  9. stirringstirred for 30 min at RT
  10. temperaturecooled down to 0° C
  11. stirringThe formed suspension was stirred for 40 min at 0° C.
  12. stirringThe reaction mixture was stirred at RT for 16 h

Sources & evidence

ORD record
ord-3710e9989b2b4e7c9dafe194155b6d99
Source dataset
uspto-grants-2010_09
Patent number
US07803790B2

Reaction notes

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