Lithium iodide → N-[2-[(3-carboxyphenyl)methoxy]-1(S)-cyanoethyl]-3-methyl-Nalpha-(diphenyacetyl)-L-phenylalaninamide

HRID 276719Notes

Reaction equation

HRID 276719 reaction equation
C[O:2][C:3]([C:5]1[CH:6]=[C:7]([CH2:11][O:12][CH2:13][C@@H:14]([NH:17][C:18](=[O:44])[C@H:19]([CH2:36][C:37]2[CH:42]=[CH:41][CH:40]=[C:39]([CH3:43])[CH:38]=2)[NH:20][C:21](=[O:35])[CH:22]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[C:15]#[N:16])[CH:8]=[CH:9][CH:10]=1)=[O:4].[I-].[Li+]>CC(=O)C(C)(C)C.C(OCC)(=O)C>[C:3]([C:5]1[CH:6]=[C:7]([CH2:11][O:12][CH2:13][C@@H:14]([NH:17][C:18](=[O:44])[C@H:19]([CH2:36][C:37]2[CH:42]=[CH:41][CH:40]=[C:39]([CH3:43])[CH:38]=2)[NH:20][C:21](=[O:35])[CH:22]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[C:15]#[N:16])[CH:8]=[CH:9][CH:10]=1)([OH:4])=[O:2]

Participants

5

Reactant 2

HCID 66321Lithium iodideHCID 86608564N-[2-[(3-(methoxycarbonyl)phenyl)methoxy]-1(S)-cyanoethyl]-3-methyl-Nalpha-(2,2-diphenylacetyl)-L-phenylalaninamide

Product 1

HCID 86608563N-[2-[(3-carboxyphenyl)methoxy]-1(S)-cyanoethyl]-3-methyl-Nalpha-(diphenyacetyl)-L-phenylalaninamide

Reagents, catalysts & solvents 2

HCID 6416PinacoloneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of N-[2-[(3-(methoxycarbonyl)phenyl)methoxy]-1(S)-cyanoethyl]-3-methyl-Nα-(2,2-diphenylacetyl)-L-phenylalaninamide (0.34 g, 0.58 mmol) in pinacolone (20 mL) is degassed with bubbling nitrogen for 10 minutes. Lithium iodide (0.78 g, 5.80 mmol) is then added, and the solution is refluxed in the dark for 24 hours, after which time it is cooled to room temperature, diluted with ethyl acetate (50 mL), and washed with 5% aq. sodium thiosulfate (2×50 mL), water (1×50 mL) and brine (1×50 mL). The organic layer is then dried over MgSO4, evaporated, and the residue is chromatographed (silica, 3% MeOH/CH2Cl2/0.05% acetic acid) to yield a clear glass, which is crystallized with an EtOAc/hexane (1:50) mixture to yield N-[2-[(3-carboxyphenyl)methoxy]-1(S)-cyanoethyl]-3-methyl-Nα-(diphenyacetyl)-L-phenylalaninamide as a white solid, m.p. 160-162° C.

Workup

  1. temperaturethe solution is refluxed in the dark for 24 hours
  2. washwashed with 5% aq. sodium thiosulfate (2×50 mL), water (1×50 mL) and brine (1×50 mL)
  3. dry with materialThe organic layer is then dried over MgSO4
  4. customevaporated
  5. customthe residue is chromatographed (silica, 3% MeOH/CH2Cl2/0.05% acetic acid)
  6. customto yield a clear glass, which
  7. customis crystallized with an EtOAc/hexane (1:50) mixture

Sources & evidence

ORD record
ord-0846df3e3fe0488bb433def1e659aba8
Source dataset
uspto-grants-2002_03
Patent number
US06353017B1

Reaction notes

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