Methanol → methyl (2R)-2-amino-3-(1H-indol-3-yl)propanoate hydrochloride
Reaction equation
[NH2:1][C@@H:2]([C:13]([OH:15])=[O:14])[CH2:3][C:4]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[NH:6][CH:5]=1.O=S(Cl)[Cl:18].[CH3:20]O>>[ClH:18].[CH3:20][O:14][C:13](=[O:15])[C@@H:2]([CH2:3][C:4]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[NH:6][CH:5]=1)[NH2:1]Participants
Procedure
D-Tryptophan (50.0 kg, 245 mol) was Suspended in MeOH (270 L), then added to a prepared solution of SOCl2 (67.0 kg, 563 mol) in MeOH (250 L) at ambient temperature under a nitrogen (N2) atmosphere. The resulting solution was stirred at reflux for 1 to 2 hours, then MeOH was distilled from the reaction mixture to about 50% of original volume. Methyl t-butyl ether (MTBE) (350 L) was added, and the solution was cooled to 0° to 5° C., with continued stirring for 1 hour. The product was filtered, washed with cold MTBE (150 L), and dried in vacuum at 60° C. to yield 57.6 kg (92.4%) of D-tryptophan methyl ester hydrochloride. 1H NM (400 MHz DMSO) δ: 11.15 (1H, s), 8.70 (2H, exch.), 7.50 (1H, d, J=8.2 Hz), 7.35 (1H, d, J=8.2 Hz), 7.24 (1H, s), 7.08-7.05 (1H, m), 7.00-6.97 (1H, m), 4.18-4.16 (1H, m), 3.61 (3H, s), 3.36-3.25 (2H, m). HPLC Details: Column: SB-Phenyl 4.6×250 mm; Eluent: Isocratic 80% (H2O+0.1% TFA)/20% ACN (acetonitrile); Temperature: 40° C.; Flow Rate=1 mL/min; UV Detection=285 nm; Injection Volume=20 μL; Diluent=1:1 ACN/H2O; and Retention Time=10.0 min.
Workup
- temperatureat reflux for 1 to 2 hours
- distillationMeOH was distilled from the reaction mixture to about 50% of original volume
- additionMethyl t-butyl ether (MTBE) (350 L) was added
- temperaturethe solution was cooled to 0° to 5° C.
- stirringwith continued stirring for 1 hour
- filtrationThe product was filtered
- washwashed with cold MTBE (150 L)
- customdried in vacuum at 60° C.
Sources & evidence
- ORD record
- ord-d790bb1d6cf84e9a8956afebdb0088f4
- Source dataset
- uspto-grants-2009_06
- Patent number
- US07550479B2
Reaction notes
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