Diisopropylethylamine → 4-([1,4]oxazepane-4-carbonyl)-1H-pyrrole-2-carboxylic acid ethyl ester

HRID 2375790Notes

Reaction equation

HRID 2375790 reaction equation
[CH3:1][O:2][C:3]([C:5]1[NH:6][CH:7]=[C:8]([C:10]([OH:12])=O)[CH:9]=1)=[O:4].Cl.[O:14]1[CH2:20][CH2:19][CH2:18][NH:17][CH2:16][CH2:15]1.[CH2:21]1CN([P+](Br)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>C(Cl)Cl>[CH2:1]([O:2][C:3]([C:5]1[NH:6][CH:7]=[C:8]([C:10]([N:17]2[CH2:18][CH2:19][CH2:20][O:14][CH2:15][CH2:16]2)=[O:12])[CH:9]=1)=[O:4])[CH3:21]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733179PyBroPHCID 124599712-Methyl 1H-pyrrole-2,4-dicarboxylateHCID 230902141,4-Oxazepane hydrochloride

Product 1

HCID 692912354-([1,4]oxazepane-4-carbonyl)-1H-pyrrole-2-carboxylic acid ethyl esterYield 116.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To 1H-pyrrole-2,4-dicarboxylic acid 2-methyl ester (291 mg) in DCM (18 mL) was added [1,4]oxazepane hydrochloride (236 mg), PyBroP (802 mg) and DIEA (878 μL). The mixture was stirred for 3 h at RT after which it was washed with saturated aqueous NaHCO3 solution and 1 N HCl. The organic phase was dried (MgSO4) and concentrated in vacuo. The residue was purified by flash column chromatography on silica (ethyl acetate) to provide 4-([1,4]oxazepane-4-carbonyl)-1H-pyrrole-2-carboxylic acid ethyl ester (533 mg). This material was used directly used in the next step although traces of phosphine oxide impurities resulting from the coupling reagent were still present.

Workup

  1. washwas washed with saturated aqueous NaHCO3 solution and 1 N HCl
  2. dry with materialThe organic phase was dried (MgSO4)
  3. concentrationconcentrated in vacuo
  4. customThe residue was purified by flash column chromatography on silica (ethyl acetate)

Sources & evidence

ORD record
ord-54482e26af2c4089944683b5d209917c
Source dataset
uspto-grants-2008_12
Patent number
US07465806B2

Reaction notes

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