Hydrochloric Acid → HCID 86589053, compound

HRID 2414379Notes

Reaction equation

HRID 2414379 reaction equation
I[C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][O:7][C:8]2=[O:9])=[CH:4][CH:3]=1.[CH3:12][C:13]1[CH:14]=[C:15]([CH:22]=[CH:23][CH:24]=1)[CH2:16][C@@H:17]([C:19]([OH:21])=[O:20])[NH2:18].Cl.C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.C(N(CC)CC)C>CC[N+](CC1C=CC=CC=1)(CC)CC.[Cl-].CN(C=O)C.CCOC(C)=O.[Cu]I.CC([O-])=O.CC([O-])=O.[Pd+2].O>[C:19]([CH:17]([NH:18][CH:6]1[C:5]2[C:10](=[CH:11][CH:2]=[CH:3][CH:4]=2)[C:8](=[O:9])[O:7]1)[CH2:16][C:15]1[CH:22]=[CH:23][CH:24]=[C:13]([CH3:12])[CH:14]=1)([OH:21])=[O:20]

Participants

12

Reactant 5

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 80271Tri-o-tolylphosphineHCID 27614943-MethylphenylalanineHCID 71741666-Iodophthalide

Product 1

HCID 86589053HCID 86589053, compound

Reagents, catalysts & solvents 6

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 66133Benzyl triethylammonium chlorideCatalystHCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 6-iodophthalide (1.0 g, 3.85 mmol), (S)-3-methylphenylalanine.HCl (0.83 g, 3.85 mmol) K2CO3 (0.53 g, 3.85 mmol), CuI (73 mg, 0.38 mmol), TEBA (0.32 g, 1.3 mmol), tri-o-tolylphosphine (0.23 g, 0.77 mmol), Pd(OAc)2 (86 mg, 0.38 mmol), triethylamine (2.14 mL, 15.38 mmol) and water (1.2 mL) in DMF (12 mL) is heated to 100° C. for 12 h. After cooling, the solution is diluted with EtOAc, and washed with 1 N HCl (100 mL), sat'd LiCl (50 mL) and water (100 mL), evaporated and chromatographed (2% MeOH/CH2Cl2, 0 to 0.05% acetic acid) to yield (S)-6-[(1-carboxy-2-(3-methylphenyl)-ethylamino]-phthalide, as a light brown foam.

Workup

  1. temperatureAfter cooling
  2. washwashed with 1 N HCl (100 mL), sat'd LiCl (50 mL) and water (100 mL)
  3. customevaporated
  4. customchromatographed (2% MeOH/CH2Cl2, 0 to 0.05% acetic acid)

Sources & evidence

ORD record
ord-3c0cc83bffe2457484d06e064a3139a2
Source dataset
uspto-grants-2004_11
Patent number
US06812237B2

Reaction notes

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