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

HRID 1849228Notes

Reaction equation

HRID 1849228 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-2627fad52b2847e5829ad1e07f9f5458
Source dataset
uspto-grants-2015_02
Patent number
US08952043B2

Reaction notes

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