Naphthoxyacetic acid → (3RS,4RS)-3-[N-((1-Naphthyloxy)Acetyl)Valinyl]Amino-5-Fluoro-4-Hydroxypentanoic Acid, tert-Butyl Ester

HRID 1066044Notes

Reaction equation

HRID 1066044 reaction equation
[C:1]1([O:11][CH2:12][C:13]([OH:15])=O)[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1.O.OC1C2N=NNC=2C=CC=1.Cl.C(N=C=NC(N)CC(C)C)C.[NH2:39][C@H:40]([C:44]([NH:46][CH:47]([CH:56]([OH:59])[CH2:57][F:58])[CH2:48][C:49]([O:51][C:52]([CH3:55])([CH3:54])[CH3:53])=[O:50])=[O:45])[CH:41]([CH3:43])[CH3:42]>CN(C)C=O.C(Cl)Cl>[C:1]1([O:11][CH2:12][C:13]([NH:39][C@H:40]([C:44]([NH:46][CH:47]([CH:56]([OH:59])[CH2:57][F:58])[CH2:48][C:49]([O:51][C:52]([CH3:53])([CH3:54])[CH3:55])=[O:50])=[O:45])[CH:41]([CH3:42])[CH3:43])=[O:15])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1

Participants

7

Reactant 4

HCID 76313Naphthoxyacetic acidHCID 221346061-Ethyl-3-(3',3'-dimethyl-1'-aminopropyl)carbodiimide hydrochlorideHCID 86584005N-(valinyl)-3-amino-4-hydroxy-5-fluoropentanoic acid, t-butyl esterHCID 178526939HCID 178526939, compound

Product 1

HCID 86585454(3RS,4RS)-3-[N-((1-Naphthyloxy)Acetyl)Valinyl]Amino-5-Fluoro-4-Hydroxypentanoic Acid, tert-Butyl EsterYield 63%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a solution of (1-naphthyloxy)acetic acid (0.202 g, 1.0 mmol) in in dimethylformamide(4.0 mL) —CH2Cl2 (6.0 mL) at 0° C. (ice bath) under nitrogen was added hydroxybenzotriazole hydrate (0.168 g) followed by 1-ethyl-3-(3′,3′-dimethyl-1′-aminopropyl)carbodiimide hydrochloride (0.249 g, 1.3 mmol). After stirring for 10 min, the mixture was treated with a solution of (3RS,4RS)-3-(valinyl)amino-5-fluoro-4-hydroxypentanoic acid, tert-butyl ester (0.319 g, 1.04 mmol) in CH2Cl2(8.0 mL). After stirring at 0° C. for 1 hr and at room temperature for 3 hrs, the mixture was partitioned between EtOAc-water. The organic phase was washed with water, 5% KHSO4, saturated NaHCO3 and saturated NaCl solutions, dried over anhydrous Na2SO4 and evaporated to dryness. The residue was purified by flash chromatography on silica gel eluting with EtOAc-hexane (3:2) to give the title compound (0.307 g, 63%) as a white solid. TLC(MeOH—CH2Cl2; 1:9) Rf=0.69.

Workup

  1. stirringAfter stirring at 0° C. for 1 hr and at room temperature for 3 hrs
  2. customthe mixture was partitioned between EtOAc-water
  3. washThe organic phase was washed with water, 5% KHSO4, saturated NaHCO3 and saturated NaCl solutions
  4. dry with materialdried over anhydrous Na2SO4
  5. customevaporated to dryness
  6. customThe residue was purified by flash chromatography on silica gel eluting with EtOAc-hexane (3:2)

Sources & evidence

ORD record
ord-b9990ca0aaad4da1ae2800795e1e2d8c
Source dataset
uspto-grants-2001_06
Patent number
US06242422B1

Reaction notes

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