4-Chloro-1-hydroxy-2-naphthoic acid → 2-[(4-Chloro-1-hydroxy-naphthalene-2-carbonyl)-amino]-2-methyl-propionic acid tert-butyl ester

HRID 2062093Notes

Reaction equation

[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([OH:12])=[C:4]([C:13]([OH:15])=O)[CH:3]=1.Cl.[C:17]([O:21][C:22](=[O:27])[C:23]([NH2:26])([CH3:25])[CH3:24])([CH3:20])([CH3:19])[CH3:18].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C)C=O.O>[C:17]([O:21][C:22](=[O:27])[C:23]([NH:26][C:13]([C:4]1[CH:3]=[C:2]([Cl:1])[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]=1[OH:12])=[O:15])([CH3:25])[CH3:24])([CH3:20])([CH3:18])[CH3:19]

Participants

Conditions

Temperature: 60 °C

Procedure

2.25 g of 4-chloro-1-hydroxy-naphthalene-2-carboxylic acid, 3.57 2-amino-2-methyl-propionic acid tert-butyl ester hydrochloride, 6.93 g HATU and 5.29 mL of N,N′diisopropylethylamine were dissolved in 100 mL of dimethylformamide. The reaction was heated at 60° C. for 1.5 hour followed by room temperature overnight. Water was added and the mixture was extracted with diethyl ether twice. The combined organic layers were dried with magnesium sulfate and concentrated in vacuo. Purification by flash chromatography on silica with heptanes/ethyl acetate afforded 1.016 g (28%) of 2-[(4-chloro-1-hydroxy-naphthalene-2-carbonyl)-amino]-2-methyl-propionic acid tert-butyl ester as a beige solid.

Workup

extractionthe mixture was extracted with diethyl ether twice
dry with materialThe combined organic layers were dried with magnesium sulfate
concentrationconcentrated in vacuo
customPurification by flash chromatography on silica with heptanes/ethyl acetate

Sources & evidence

ORD record: ord-3f5a1be694b4499f856d18eb57c0fec9
Source dataset: uspto-grants-2012_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08283479B2

Reaction notes

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