Methanesulfonic Acid → Nelfinavir Mesylate

HRID 395908Notes

Reaction equation

HRID 395908 reaction equation
[CH3:1][C:2]1[C:7]([OH:8])=[CH:6][CH:5]=[CH:4][C:3]=1[C:9]([NH:11][C@H:12]([C@H:21]([OH:40])[CH2:22][N:23]1[C@H:32]([C:33]([NH:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[CH2:31][C@H:30]2[C@H:25]([CH2:26][CH2:27][CH2:28][CH2:29]2)[CH2:24]1)[CH2:13][S:14][C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1)=[O:10].[CH3:41][S:42]([OH:45])(=[O:44])=[O:43]>O1CCCC1>[CH3:1][C:2]1[C:7]([OH:8])=[CH:6][CH:5]=[CH:4][C:3]=1[C:9]([NH:11][C@H:12]([C@H:21]([OH:40])[CH2:22][N:23]1[C@H:32]([C:33]([NH:35][C:36]([CH3:38])([CH3:37])[CH3:39])=[O:34])[CH2:31][C@H:30]2[C@H:25]([CH2:26][CH2:27][CH2:28][CH2:29]2)[CH2:24]1)[CH2:13][S:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)=[O:10].[CH3:41][S:42]([OH:45])(=[O:44])=[O:43]

Participants

4

Reactant 2

HCID 6395Methanesulfonic AcidHCID 64143Nelfinavir

Product 1

HCID 64142Nelfinavir Mesylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Nelfinavir free base (10.2 kg, 18.0 mol) and 24 L of tetrahydrofuran were added to a 100L reactor. Methanesulfonic acid (1.8 kg, 18.48 mol) also was added to the reactor. The reactor was stirred until all solids dissolved, and then the solution was filtered into a 100 gallon polypropylene tank containing 306 L methyl t-butyl ether or diethyl ether that was rapidly stirring. After stirring for 2 hours, the 100 gallon tank contents were filtered, washed with 17 L of methyl t-butyl ether or diethyl ether, and pulled as dry as possible. The solid was transferred to a rotocone drier and dried in a vacuum oven at 60-65° C. (at least 26 in. Hg or higher vacuum) for 12-72 hours or until the methyl t-butyl ether or diethyl ether content of the dried solid was below 1%. If necessary, the drier contents could be milled in a Fitzmill grinder to accelerate drying. Typical yields of nelfinavir mesylate range from 9 to 11 kg. (76%-92% theory).

Workup

  1. dissolutiondissolved
  2. filtrationthe solution was filtered into a 100 gallon polypropylene tank
  3. additioncontaining 306 L methyl t-butyl ether or diethyl ether that
  4. stirringwas rapidly stirring
  5. stirringAfter stirring for 2 hours
  6. filtrationthe 100 gallon tank contents were filtered
  7. washwashed with 17 L of methyl t-butyl ether or diethyl ether
  8. customas dry as possible
  9. customdried in a vacuum oven at 60-65° C. (at least 26 in. Hg or higher vacuum) for 12-72 hours
  10. customIf necessary, the drier contents could be milled in a Fitzmill grinder
  11. customto accelerate drying

Sources & evidence

ORD record
ord-34c6e81b03ca44ba9a4cc6c353d0b35c
Source dataset
uspto-grants-2003_08
Patent number
US06605721B2

Reaction notes

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