Acetic Acid → HCID 178476474, compound

HRID 734911Notes

Reaction equation

HRID 734911 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[CH:25]([O:27][C:28](Cl)=[O:29])[CH3:26].[C:31]([OH:34])(=[O:33])[CH3:32]>ClCCl>[C:31]([O:34][CH:25]([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])[CH3:26])(=[O:33])[CH3:32]

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 6397ChlorotrimethylsilaneHCID 79724-Methylmorpholine2×HCID 5213051-Chloroethyl chloroformateHCID 178511262HCID 178511262, compound

Product 1

HCID 178476474HCID 178476474, compoundYield 22.3%

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 1-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 acetic acid (2.86 mL, 3.00 g, 50 mmol) yielded the title compound 8 (320 mg, 22% yield) as a very slightly orange-colored oil after aqueous work-up and mass-guided preparative HPLC purification. 1H NMR (400 MHz, DMSO-d6): δ=0.82-0.94 (br. m, 2H), 1.17-1.35 (br. m, 3H), 1.38 (d, J=5.2 Hz, 3H), 1.66-1.73 (br. m, 2H), 1.84-1.91 (br. m, 2H), 1.99 (s, 3H), 2.10 (tt, J=12.0, 3.6 Hz, 1H), 2.74-2.88 (m, 2H), 6.62 (q, J=5.2 Hz, 1H), 7.44 (t, J=6.0 Hz, 1H), 11.97 (br. s, 1H). MS (ESI) m/z 310.12 (M+Na)+; 286.08 (M−H)−.

Sources & evidence

ORD record
ord-43f706e3f5ae492c8404317b167714ee
Source dataset
uspto-grants-2009_09
Patent number
US07592369B2

Reaction notes

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