Propionic Acid → HCID 178460509, compound

HRID 734912Notes

Reaction equation

HRID 734912 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-d429c7d62b6d49a6b6edd7ab1b56f8f6
Source dataset
uspto-grants-2009_09
Patent number
US07592369B2

Reaction notes

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