Hydrochloric Acid → 5-(Tert-butoxycarbonylamino)-2-(butyryloxy)benzoic acid

HRID 716671Notes

Reaction equation

C(N(C(C)C)CC)(C)C.[C:10](Cl)(=[O:14])[CH2:11][CH2:12][CH3:13].[C:16]([O:20][C:21]([NH:23][C:24]1[CH:25]=[CH:26][C:27]([OH:33])=[C:28]([CH:32]=1)[C:29]([OH:31])=[O:30])=[O:22])([CH3:19])([CH3:18])[CH3:17].Cl.Cl.CCOCC>ClCCl.C(OCC)C>[C:16]([O:20][C:21]([NH:23][C:24]1[CH:25]=[CH:26][C:27]([O:33][C:10](=[O:14])[CH2:11][CH2:12][CH3:13])=[C:28]([CH:32]=1)[C:29]([OH:31])=[O:30])=[O:22])([CH3:19])([CH3:17])[CH3:18]

Participants

Conditions

Temperature: 0 °C

Procedure

Diisopropylethylamine (3 eq) (complete dissolution) followed by butyryl chloride (2 eq) is added to a suspension of about 0.4 M of the compound (II) in dichloromethane, cooled to 0° C. and in inert atmosphere. It is stirred at ambient temperature for 16 hours. HCl 1N (cooled in an ice bath) up to acid pH is added. The organic phase is washed with water, anhydrified and evaporated. At this stage a mixture of the desired product (III) and deacylated product (probably the corresponding anhydride) is obtained as a whitish solid. The mixture is dissolved in ethyl ether (concentration of about 0.1 M), a 2N solution of HCl in ethyl ether (0.2 eq) is added and it is stirred at ambient temperature for 25 days, during which 2N hydrochloride ether is added other 2 times (0.4 eq HCl totally) up to obtaining complete conversion in the product (III). The solvent is evaporated, the resulting solid is triturated with hexane (2 times), it is filtered and it is dried, obtaining the product (III) as white solid. 88% yield, LC-MS 99% purity.

Workup

washThe organic phase is washed with water
customevaporated
additionAt this stage a mixture of the desired product (III) and deacylated product (probably the corresponding anhydride)
customis obtained as a whitish solid

Sources & evidence

ORD record: ord-5b373221f5f94c76b729b15adef5c320
Source dataset: uspto-grants-2015_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09193673B2

Reaction notes

Loading…