Hydrochloric Acid → Melphalan

HRID 1411207Notes

Reaction equation

HRID 1411207 reaction equation
Cl.Cl.C[O:4][C:5](=[O:22])[C@H:6]([CH2:8][C:9]1[CH:14]=[CH:13][C:12]([N:15]([CH2:19][CH2:20][Cl:21])[CH2:16][CH2:17][Cl:18])=[CH:11][CH:10]=1)[NH2:7]>>[Cl:18][CH2:17][CH2:16][N:15]([CH2:19][CH2:20][Cl:21])[C:12]1[CH:11]=[CH:10][C:9]([CH2:8][C@@H:6]([C:5]([OH:22])=[O:4])[NH2:7])=[CH:14][CH:13]=1

Participants

3

Reactant 2

HCID 313Hydrochloric AcidHCID 2114446962978-52-3

Product 1

HCID 460612Melphalan

Conditions

Temperature
0 °C

Procedure

Concentrated hydrochloric acid (425 ml, 5 volume) was added to the crude 4-[bis(2-chloroethyl)-amino]-L-phenylalanine methyl ester hydrochloride (III) obtained in Example 1 and the reaction mixture was heated at 80° C. to 85° C. After completion of the reaction, as monitored by HPLC, the mixture was treated with activated carbon and filtered through hyflo bed. The filtrate was cooled to 0° C. and the pH of the filtrate was adjusted to pH 6.0 by addition of aqueous ammonia solution (450 ml). The product was filtered, washed with water and the wet 4-[bis(2-chloroethyl)-amino]-L-phenylalanine free base (IV) was used as such for preparation of the hydrochloride salt.

Workup

  1. temperaturethe reaction mixture was heated at 80° C. to 85° C
  2. customAfter completion of the reaction
  3. additionthe mixture was treated with activated carbon
  4. filtrationfiltered through hyflo bed
  5. additionthe pH of the filtrate was adjusted to pH 6.0 by addition of aqueous ammonia solution (450 ml)
  6. filtrationThe product was filtered
  7. washwashed with water
  8. customsuch for preparation of the hydrochloride salt

Sources & evidence

ORD record
ord-2a31ad48d6b14cc0811c03628a5b6f67
Source dataset
uspto-grants-2014_12
Patent number
US08921596B2

Reaction notes

Loading…