Diisopropylethylamine → HCID 68697269, compound

HRID 2235100Notes

Reaction equation

HRID 2235100 reaction equation
F[P-](F)(F)(F)(F)F.Br[P+](N1CCCC1)(N1CCCC1)N1CCCC1.C(N(C(C)C)CC)(C)C.C(OC([N:41]1[C:49]2[C:44](=[C:45]([O:53][CH3:54])[CH:46]=[C:47]([C:50]([OH:52])=O)[CH:48]=2)[CH2:43][CH2:42]1)=O)(C)(C)C.[CH2:55]([O:57][C:58](=[O:67])[C:59]1[CH:64]=[CH:63][C:62]([NH2:65])=[CH:61][C:60]=1[F:66])[CH3:56]>O1CCCC1>[CH2:55]([O:57][C:58](=[O:67])[C:59]1[CH:64]=[CH:63][C:62]([NH:65][C:50]([C:47]2[CH:48]=[C:49]3[C:44]([CH2:43][CH2:42][NH:41]3)=[C:45]([O:53][CH3:54])[CH:46]=2)=[O:52])=[CH:61][C:60]=1[F:66])[CH3:56]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733179PyBroPHCID 10797532Ethyl 4-Amino-2-fluorobenzoateHCID 68698202HCID 68698202, compound

Product 1

HCID 68697269HCID 68697269, compoundYield 27%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Bromo-tris-pyrrolidino-phosphonium hexafluorophosphate (0.874 g, 1.88 mmol, 1.1 equiv.) and diisopropyl ethyl amine (0.46 mL, 3.58 mmol, 2.1 equiv.) were added to a solution of 4-methoxy-2,3-dihydro-indole-1,6-dicarboxylic acid 1-tert-butyl ester (0.500 g, 1.7 mmol, 1 equiv.) in tetrahydrofuran (10 mL) and the mixture was shaken for 5 minutes at room temperature. 4-Amino-2-fluorobenzoic acid ethyl ester (3.433 g 1.88 mmol, 1.1 equiv.) was added and the mixture shaken at room temperature for 16 hours. The solvent was removed under vacuum and the residue dissolved in trifluoroacetic acid (10 mL) and shaken for 1 hour at room temperature. The solvent was removed under vacuum and the residue was purified by column chromatography (SiO2, 1:1 Hept/EtOAc to EtOAc). The fractions were combined to afford crude 2-fluoro-4-[(4-methoxy-2,3-dihydro-1H-indole-6-carbonyl)-amino]-benzoic acid ethyl ester, 0.476 g (27% yield), this material was taken onto the next step without further purification. LC @215 nm; Rt 1.17: 46%, m/z (ES+): 359 (M+H+.).

Workup

  1. stirringthe mixture shaken at room temperature for 16 hours
  2. customThe solvent was removed under vacuum
  3. dissolutionthe residue dissolved in trifluoroacetic acid (10 mL)
  4. stirringshaken for 1 hour at room temperature
  5. customThe solvent was removed under vacuum
  6. customthe residue was purified by column chromatography (SiO2, 1:1 Hept/EtOAc to EtOAc)

Sources & evidence

ORD record
ord-68d5944915bc46f0b3fd26e2c1bc35eb
Source dataset
uspto-grants-2010_05
Patent number
US07713996B2

Reaction notes

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