Pyridine → Methyl 3-(8-bromo-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamido)-4-chlorobenzoate

HRID 1190507Notes

Reaction equation

HRID 1190507 reaction equation
[Br:1][C:2]1[CH:18]=[CH:17][C:5]2[C:6]3[S:7][C:8]([C:14]([OH:16])=O)=[CH:9][C:10]=3[CH2:11][CH2:12][O:13][C:4]=2[CH:3]=1.[CH3:19][O:20][C:21](=[O:30])[C:22]1[CH:27]=[CH:26][C:25]([Cl:28])=[C:24]([NH2:29])[CH:23]=1.N1C=CC=CC=1>O=S(Cl)Cl.C1COCC1>[Br:1][C:2]1[CH:18]=[CH:17][C:5]2[C:6]3[S:7][C:8]([C:14]([NH:29][C:24]4[CH:23]=[C:22]([CH:27]=[CH:26][C:25]=4[Cl:28])[C:21]([O:20][CH3:19])=[O:30])=[O:16])=[CH:9][C:10]=3[CH2:11][CH2:12][O:13][C:4]=2[CH:3]=1

Participants

6

Reactant 3

HCID 1049PyridineHCID 593055Methyl 3-Amino-4-chlorobenzoateHCID 579001638-Bromo-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxylic acid

Product 1

HCID 56834370Methyl 3-(8-bromo-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamido)-4-chlorobenzoateYield 87%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 24386Thionyl ChlorideSolvent

Procedure

A solution of 8-bromo-4,5-dihydro-6-oxa-1-thia-benzo[e]azulene-2-carboxylic acid (25 g, 0.077 mol) in 200 mL of SOCl2 was heated at 80° C. for 3 h. Concentration gave the crude acid chloride. A suspension of the crude acid chloride (ca. 0.077 mol) from above in 1000 mL of THF at 0° C. was treated with a solution of 3-amino-4-chloro-benzoic acid methyl ester (15.7 g, 1.1 eq)/pyridine (30 mL) in 100 mL of THF. The mixture was allowed to reach room temperature overnight. The reaction solution was concentrated to ½ volume, diluted with water. The resulting precipitate was filtered, washed with water and Et2O. The filter cake was dried to a constant weight under vacuum to give methyl 3-(8-bromo-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamido)-4-chlorobenzoate (32.9 g, yield 87%). LC-MS: (ESI, m/z)=494 [M+1]+

Workup

  1. concentrationConcentration
  2. customgave the crude acid chloride
  3. concentrationThe reaction solution was concentrated
  4. additiondiluted with water
  5. filtrationThe resulting precipitate was filtered
  6. washwashed with water and Et2O
  7. customThe filter cake was dried to a constant weight under vacuum

Sources & evidence

ORD record
ord-4bcf24b215dc4a5e955daf9b006b7700
Source dataset
uspto-grants-2014_03
Patent number
US08673952B2

Reaction notes

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