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

HRID 1371288Notes

Reaction equation

HRID 1371288 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-f7549bf6f70145ae867816c8b63e27a3
Source dataset
uspto-grants-2007_01
Patent number
US07157430B2

Reaction notes

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