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

HRID 708051Notes

Reaction equation

HRID 708051 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 1/2 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 to 1/2 volume
  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-20ab25c75bc94ea59d122ddbf02d33e5
Source dataset
uspto-grants-2015_11
Patent number
US09175009B2

Reaction notes

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