L-Phenylalanine → HCID 70079233, compound

HRID 1955680Notes

Reaction equation

HRID 1955680 reaction equation
[NH2:1][C@H:2]([C:10]([OH:12])=O)[CH2:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[CH3:13][N:14]1[CH2:19][CH2:18][O:17][CH2:16][CH2:15]1.ClC(OCC(C)C)=[O:22].Cl.[NH2:29][CH:30]([CH2:42][CH2:43][C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1)[CH:31]=[CH:32][C:33]1[CH:38]=[CH:37][C:36]([N+:39]([O-:41])=[O:40])=[CH:35][CH:34]=1.Cl.O1CCOCC1.C(OC(NC(CCC1C=CC=CC=1)C=CC1C=CC([N+]([O-])=O)=CC=1)=O)(C)(C)C>C1COCC1.C(Cl)Cl>[N:14]1([C:13]([C:7]2[CH:6]=[CH:5][C:4]([CH2:3][C@@H:2]([C:10]([NH:29][C@@H:30]([CH2:42][CH2:43][C:44]3[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=3)[CH:31]=[CH:32][C:33]3[CH:38]=[CH:37][C:36]([N+:39]([O-:41])=[O:40])=[CH:35][CH:34]=3)=[O:12])[NH2:1])=[CH:9][CH:8]=2)=[O:22])[CH2:19][CH2:18][O:17][CH2:16][CH2:15]1

Participants

9

Reactant 6

HCID 6140L-PhenylalanineHCID 79724-Methylmorpholine2×HCID 62365Isobutyl chloroformateHCID 204431481,4-Dioxane hydrochlorideHCID 53906518HCID 53906518, compoundHCID 77776311HCID 77776311, compound

Product 1

HCID 70079233HCID 70079233, compoundYield 40%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of Mu-PheOH (1.29 g, 4.63 mmol) in THF (20 mL) were added 4-methylmorpholine (0.51 mL, 4.63 mmol) and isobutyl chloroformate (0.61 mL, 4.63 mmol). After 3 minutes, a solution of (S) 3-amino-1-(4-nitrophenyl)-5-phenyl-1-pentene hydrochloride, prepared by HCl/dioxane-mediated deprotection of (S) 3-tert-butoxycarbonylamino-1-(4-nitrophenyl)-5-phenyl-1-pentene precursor, 1.34 g, 4.20 mmol) in CH2Cl2 (20 mL), followed by 4-methylmorpholine (0.51 mL, 4.63 mmol). The mixture was stirred overnight while warming to room temperature. The solution mixture was diluted with CH2Cl2 (100 mL), washed with 1M HCl (200 mL), saturated aqueous sodium bicarbonate (200 mL); dried over MgSO4, filtered, and concentrated under reduced pressure to give a yellow oil. This material was crystallized from CH2Cl2 /ether (2:100, 20 mL) to give 1.00 g (40%) of (S)-3-(4-morpholinecarbonylphenylalanyl)amino-1-(4-nitrophenyl)-5-phenyl-1-pentene as an approximately 4:1 E/Z mixture. 0.27 g (0.49 mmol) of this material was dissolved in ethanol (50 mL), transferred to a Parr bottle charged with 5% palladium on carbon (0.10 g) and reduced on a Parr hydrogenator for 8 hours/ The mixture was filtered and the solvent was removed under reduced pressure. The residue was dissolved in in 4:1 ether/CH2Cl2 (100 mL), to which HCl/dioxane (0.136 mL of a 4.0M solution) was added. The product, Mu-Phe-Hph-γ-C6H4 NH2.HCl, was filtered and dried in vacuo. Yield=0.15 g (54%). TLC: (10% methanol/CH2Cl2) Rf =0.31.

Workup

  1. washwashed with 1M HCl (200 mL), saturated aqueous sodium bicarbonate (200 mL)
  2. dry with materialdried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customto give a yellow oil
  6. customThis material was crystallized from CH2Cl2 /ether (2:100, 20 mL)

Sources & evidence

ORD record
ord-5524d736504e47019c298e2ae15ab596
Source dataset
uspto-grants-1998_07
Patent number
US05776718

Reaction notes

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