Formic Acid → Boc-Leu-Leu-Lys(Z)-Leu-Leu-OH

HRID 2298449Notes

Reaction equation

HRID 2298449 reaction equation
[OH-].[Na+].[NH:3]([C:56]([O:58][C:59]([CH3:62])([CH3:61])[CH3:60])=[O:57])[C@H:4]([C:9]([NH:11][C@H:12]([C:17]([NH:19][C@H:20]([C:36]([NH:38][C@H:39]([C:44]([NH:46][C@H:47]([C:52]([O:54]C)=[O:53])[CH2:48][CH:49]([CH3:51])[CH3:50])=[O:45])[CH2:40][CH:41]([CH3:43])[CH3:42])=[O:37])[CH2:21][CH2:22][CH2:23][CH2:24][NH:25][C:26]([O:28][CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)=[O:27])=[O:18])[CH2:13][CH:14]([CH3:16])[CH3:15])=[O:10])[CH2:5][CH:6]([CH3:8])[CH3:7].C1COCC1.C(O)=O>O.C(OCC)(=O)C>[NH:3]([C:56]([O:58][C:59]([CH3:62])([CH3:61])[CH3:60])=[O:57])[C@H:4]([C:9]([NH:11][C@H:12]([C:17]([NH:19][C@H:20]([C:36]([NH:38][C@H:39]([C:44]([NH:46][C@H:47]([C:52]([OH:54])=[O:53])[CH2:48][CH:49]([CH3:50])[CH3:51])=[O:45])[CH2:40][CH:41]([CH3:42])[CH3:43])=[O:37])[CH2:21][CH2:22][CH2:23][CH2:24][NH:25][C:26]([O:28][CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)=[O:27])=[O:18])[CH2:13][CH:14]([CH3:16])[CH3:15])=[O:10])[CH2:5][CH:6]([CH3:8])[CH3:7]

Participants

7

Reactant 4

HCID 284Formic AcidHCID 8028TetrahydrofuranHCID 14798Sodium HydroxideHCID 12020547Boc-Leu-Leu-Lys(Z)-Leu-Leu-OMe

Product 1

HCID 12020548Boc-Leu-Leu-Lys(Z)-Leu-Leu-OHYield 97.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
62.5 °C

Procedure

A solution of NaOH(1.44 g, 36.0 mmol) in H2O (15.0 g) was added at 20-25° C. over 5 min to a mixture of Boc-Leu-Leu-Lys(Z)-Leu-Leu-OMe (SEQ. ID No. 2) (12.0 g, 14.16 mmol) THF (48.0 g) and H2O (18.0 g). The resulting mixture was stirred for 2 h. 98% Formic acid (5 g) was added, followed by ethyl acetate (30.0 g). The resulting organic phase was washed with H2O, concentrated in vacuo and the residue was dissolved in MeOH (60.0 g). The solids were filtered and rinsed with an additional portion of MeOH (8.0 g). The combined MeOH solution was heated to 60-65° C. and H2O (30.0 g) was added over 10 min. This mixture was cooled to 20-25° C., the solid product began to crystallize. An additional portion of H2O (35.0 g) was added and the mixture was stirred for 1 h. The solid product was filtered, washed with H2O and dried in vacuo to give Boc-Leu-Leu-Lys(Z)-Leu-Leu-OH (SEQ. ID No. 2) (11.5 g, 97.5%).

Workup

  1. washThe resulting organic phase was washed with H2O
  2. concentrationconcentrated in vacuo
  3. dissolutionthe residue was dissolved in MeOH (60.0 g)
  4. filtrationThe solids were filtered
  5. washrinsed with an additional portion of MeOH (8.0 g)
  6. additionH2O (30.0 g) was added over 10 min
  7. temperatureThis mixture was cooled to 20-25° C.
  8. customto crystallize
  9. additionAn additional portion of H2O (35.0 g) was added
  10. stirringthe mixture was stirred for 1 h
  11. filtrationThe solid product was filtered
  12. washwashed with H2O
  13. customdried in vacuo

Sources & evidence

ORD record
ord-a24bf1aa912b47238f6d0e91d53a75d4
Source dataset
uspto-grants-2002_12
Patent number
US06492490B1

Reaction notes

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