Propionic Acid → HCID 178460509, compound

HRID 386936Notes

Reaction equation

HRID 386936 reaction equation
[CH2:1]1[CH2:6][C@H:5]([C:7]([OH:9])=[O:8])[CH2:4][CH2:3][C@H:2]1[CH2:10][NH2:11].Cl[Si](C)(C)C.CN1CCOCC1.Cl[CH2:25][CH2:26][O:27][C:28](Cl)=[O:29].[C:31]([OH:35])(=[O:34])[CH2:32][CH3:33]>ClCCl>[C:31]([O:35][CH:26]([O:27][C:28]([NH:11][CH2:10][C@H:2]1[CH2:3][CH2:4][C@H:5]([C:7]([OH:9])=[O:8])[CH2:6][CH2:1]1)=[O:29])[CH3:25])(=[O:34])[CH2:32][CH3:33]

Participants

7

Reactant 5

HCID 1032Propionic AcidHCID 6397ChlorotrimethylsilaneHCID 79724-Methylmorpholine2×HCID 123052-Chloroethyl chloroformateHCID 178511262HCID 178511262, compound

Product 1

HCID 178460509HCID 178460509, compoundYield 7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Following the general procedure for the one pot synthesis, tranexamic acid (786 mg, 5.0 mmol) was reacted with chlorotrimethylsilane (1.396 mL, 1.195 g, 11.0 mmol) in anhydrous dichloromethane (10 mL) and in the presence of N-methylmorpholine (1.374 mL, 1.264 g, 12.5 mmol). Subsequent reaction of the intermediate with chloroethylchloroformate (0.82 mL, 1.07 g, 7.5 mmol) followed by a mixture of NMM (2.75 mL, 2.53 g, 25 mmol) and propionic acid (3.73 mL, 3.70 g, 50 mmol) yielded the title compound 9 (103 mg, 7% yield) as colorless, very viscous oil after aqueous work-up and two mass-guided preparative HPLC purifications. 1H NMR (400 MHz, DMSO-d6): δ=0.82-0.94 (br. m, 2H), 1.03 (t, J=7.6 Hz, 3H), 1.17-1.35 (br. m, 3H), 1.38 (d, J=5,2 Hz, 3H), 1.65-1.73 (br. m, 2H), 1.83-1.91 (br. m, 2H), 2.09 (tt, J=12.4, 3.6 Hz, 1H), 2.26-2.33 (m, 2H), 2.74-2.90 (m, 2H), 6.64 (q, J=5.6 Hz, 1H), 7.44 (t, J=5.6 Hz, 1H), 11.99 (br. s, 1H). MS (ESI) m/z 324.14 (M+Na)+; 300.10 (M−H)−.

Sources & evidence

ORD record
ord-1cc08022dbd247b39d8ef637a05ba0d1
Source dataset
uspto-grants-2013_02
Patent number
US08372881B2

Reaction notes

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