Benzyl chloroformate → HCID 18512823, compound

HRID 492659Notes

Reaction equation

HRID 492659 reaction equation
[NH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][C:25]([OH:27])=[O:26].C1CCN2C(=NCCC2)CC1.[CH2:39]([O:46][C:47](Cl)=[O:48])[C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1>CO>[CH2:39]([O:46][C:47]([NH:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][C:25]([OH:27])=[O:26])=[O:48])[C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1

Participants

5

Reactant 3

HCID 10387Benzyl chloroformateHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 18512762HCID 18512762, compound2×

Product 1

HCID 18512823HCID 18512823, compoundYield 87%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To D6 (0.500 g, 1.30 mmol) and DBU (794 mg, 5.21 mmol) in refluxing methanol (100 ml) was added neat benzylchloroformate and the reaction refluxed for 3 hours until complete conversion of D6 to either the protected amino acid D19 or its methyl ester was observed. The solvent was removed and the residues taken up into dioxane (60 ml) and water (2 ml) and lithium hydroxide (1 g) added. The reaction was then refluxed for 2 hours until hydrolysis of the methyl ester derivative to D19 was complete. The solvent was removed, the residues suspended in 1M HCl (100 ml) and extracted with hot ethyl acetate (300 ml). The hot ethyl acetate was dried (MgSO4) and the solvent volume reduced to 40 ml. The solution/suspension was left at −10° C. for 1 hour, allowed to warm to room temperature and the resulting white precipitates filtered off and dried under vacuum to yield the title compound (585 mg, 87%). M.Pt 102-104° C. C32H55NO4 requires 517.4. Found ES−: MCI−, 552.6. δH (d6DMSO), 1.32 (38H, s, (CH2)19(CH2)2N), 1.52 (2H, p, CH2CH2CO2H), 1.65 (2H, p, CH2CH2NH), 2.35 (2H, t, CH2CO2H), 3.18 (2H, t, CH2N), 5.14 (2H, s, CH2Ph), 7.35 (5H, m, Ph).

Workup

  1. customThe solvent was removed
  2. additionadded
  3. temperatureThe reaction was then refluxed for 2 hours until hydrolysis of the methyl ester derivative to D19 was complete
  4. customThe solvent was removed
  5. extractionextracted with hot ethyl acetate (300 ml)
  6. dry with materialThe hot ethyl acetate was dried (MgSO4)
  7. customthe resulting white precipitates
  8. filtrationfiltered off
  9. customdried under vacuum

Sources & evidence

ORD record
ord-a6d5d0e15e824e8e934d8a11218e93a9
Source dataset
uspto-grants-2009_05
Patent number
US07531676B2

Reaction notes

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