4-Chlorobenzoyl chloride → HCID 15167815, compound

HRID 1084554Notes

Reaction equation

HRID 1084554 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=2[NH:12][C:11](=[O:19])[CH:10]([OH:20])[N:9]=1.[Cl:21][C:22]1[CH:30]=[CH:29][C:25]([C:26](Cl)=[O:27])=[CH:24][CH:23]=1>C(Cl)Cl.CN(C)C1C=CN=CC=1>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=2[NH:12][C:11](=[O:19])[CH:10]([O:20][C:26](=[O:27])[C:25]2[CH:29]=[CH:30][C:22]([Cl:21])=[CH:23][CH:24]=2)[N:9]=1

Participants

5

Reactant 2

HCID 85014-Chlorobenzoyl chloride2×HCID 15167814HCID 15167814, compound

Product 1

HCID 15167815HCID 15167815, compound

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalyst2×HCID 6344DichloromethaneSolvent2×

Procedure

A suspension of 1,3-dihydro-5-(2-fluorophenyl)-3-hydroxy-2H-1,4-benzodiazepin-2-one (610 mg, 2.25 mmole) in 25 ml of methylene chloride was treated with 4-chlorobenzoyl chloride (0.314 ml, 2.48 mmole) at room temperature. 4-Dimethylaminopyridine (303 mg, 2.48 mmole) was added and within minutes the reaction mixture became homogeneous. The reaction mixture was protected from moisture and stirred at room temperature overnight. An additional equivalent each of 4-chlorobenzoyl chloride and 4-dimethylaminopyridine were added and stirring was continued for 8 hours at 40°-45° C. The reaction mixture was diluted to 150 ml with methylene chloride and washed in succession with 10% citric acid solution (3×50 ml), saturated sodium bicarbonate solution (3×50 ml) and brine (50 ml). Rotoevaporation of the dried (MgSO4) organic phase gave a foam which on trituration with ether afforded a beige solid. The mother liquors were concentrated and the residue chromatographed on silica gel (hexane-ethyl acetate, 1:1 v/v) to give the title compound.

Workup

  1. stirringstirring
  2. waitwas continued for 8 hours at 40°-45° C
  3. washwashed in succession with 10% citric acid solution (3×50 ml), saturated sodium bicarbonate solution (3×50 ml) and brine (50 ml)
  4. dry with materialRotoevaporation of the dried (MgSO4) organic phase
  5. customgave a foam which on trituration with ether
  6. customafforded a beige solid
  7. concentrationThe mother liquors were concentrated
  8. customthe residue chromatographed on silica gel (hexane-ethyl acetate, 1:1 v/v)

Sources & evidence

ORD record
ord-e707a10782a54a84a16ecd250c98ceb2
Source dataset
uspto-grants-1991_04
Patent number
US05004741

Reaction notes

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