Diethyl Ether → N-Boc-Tyr(Bn)-Ala-Trp-OH

HRID 2074365Notes

Reaction equation

HRID 2074365 reaction equation
[NH:1]([C:41]([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:42])[C@H:2]([C:18]([NH:20][C@H:21]([C:23]([NH:25][C@H:26]([C:37]([O:39]C)=[O:38])[CH2:27][C:28]1[C:36]2[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=2)[NH:30][CH:29]=1)=[O:24])[CH3:22])=[O:19])[CH2:3][C:4]1[CH:9]=[CH:8][C:7]([O:10][CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[CH:6][CH:5]=1.[Li+].[OH-].C1(NC2CCCCC2)CCCCC1.CCOCC>C1COCC1.CO>[NH:1]([C:41]([O:43][C:44]([CH3:45])([CH3:47])[CH3:46])=[O:42])[C@H:2]([C:18]([NH:20][C@H:21]([C:23]([NH:25][C@H:26]([C:37]([OH:39])=[O:38])[CH2:27][C:28]1[C:36]2[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=2)[NH:30][CH:29]=1)=[O:24])[CH3:22])=[O:19])[CH2:3][C:4]1[CH:9]=[CH:8][C:7]([O:10][CH2:11][C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=2)=[CH:6][CH:5]=1

Participants

7

Reactant 4

HCID 3283Diethyl EtherHCID 3939Lithium HydroxideHCID 7582DicyclohexylamineHCID 44424692N-Boc-Tyr(Bn)-Ala-Trp-OMe

Product 1

HCID 44424695N-Boc-Tyr(Bn)-Ala-Trp-OHYield 64%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

compound NR66. Saponification of N-Boc-Tyr(Bn)-Ala-Trp-OMe (580 mg, 0.902 mmol) in THF (5 mL) by 1 M aqueous LiOH (2 mL, 2 mmol) at 4° C. for 1 hour, afforded after acidic treatment and precipitation of the residue with water crude N-Boc-Tyr(Bn)-Gly-Trp-OH. The crude product in MeOH (0.5 mL) was treated by dicyclohexylamine (0.18 mL, 0.91 mmol) and then ether (10 mL). After filtration, the resulting solid was dissolved in CH2Cl2 (10 mL) and washed by 10% aqueous citric acid. The organic phase was dried over MgSO4 and concentrated to afford N-Boc-Tyr(Bn)-Ala-Trp-OH (361 mg, 64%) as a white solid. 1H NMR (300 MHz, DMSO-d6) δ 1.20 (d, J=7 Hz, 3H, CH3), 1.28 (s, 9H, (CH3)3), 2.62 and 2.86 (ABX system, 2H, CH2β), 3.09 and 3.18 (ABX system, 2H, CH2β), 4.10 (m, 1H, CHα), 4.35 (m, 1H, CHα), 4.46 (m, 1H, CHα), 5.03 (s, 2H, CH2 (OBn)), 6.87-7.54 (m, 15H, 14 aromatic H+1 NH), 7.96 (d, J=7.5 Hz, 1H), 8.13 (d, J=7.5 Hz, 1H), 10.84 (s, 1NH). 13C NMR (75 MHz, CDCl3) δ 18.2 (CH3), 27.2 (CH2 Trp), 28.3 ((CH3)3), 37.3 (CH2 Tyr), 48.9, 53.3, 55.7 (CHα Ala, Tyr or Trp), 70.0 (CH2 (OBn)), 80.7 (C(CH3)3), 109.5 (aromatic C), 111.5, 115.0, 118.6, 119.5, 121.9, 123.8, 127.5, 127.6, 128.1, 128.6, 130.4 (aromatic CH), 136.1, 137.0, 137.1 (aromatic C), 155.8, 157.8 (Car-O or CO carbamate), 171.9, 172.3, 174.2 (2 CO amide or CO acid). Anal. Calcd. for C35H40N4O7, 1.5H2O: C, 64.11%; H, 6.61%; N, 8.54%. Found: C, 64.19%; H, 6.36%; N, 8.79%.

Workup

  1. customafforded
  2. customafter acidic treatment and precipitation of the residue with water crude N-Boc-Tyr(Bn)-Gly-Trp-OH
  3. filtrationAfter filtration
  4. dissolutionthe resulting solid was dissolved in CH2Cl2 (10 mL)
  5. washwashed by 10% aqueous citric acid
  6. dry with materialThe organic phase was dried over MgSO4
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-3722f71ad7554e35a90b5dfcbf4e3102
Source dataset
uspto-grants-2011_04
Patent number
US07919468B2

Reaction notes

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