Dicyclohexylcarbodiimide → HCID 131720724, compound

HRID 964492Notes

Reaction equation

HRID 964492 reaction equation
[NH:1]([C:6]([O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)=[O:7])[CH2:2][C:3]([OH:5])=O.C1CCC(N=C=NC2CCCCC2)CC1.[NH2:31][C@H:32]([C:41]([NH:43][CH2:44][C:45]([OH:47])=[O:46])=[O:42])[CH2:33][C:34](=[O:40])[O:35][C:36]([CH3:39])([CH3:38])[CH3:37].C([O-])(O)=O.[Na+].N(C(OCC1C=CC=CC=1)=O)CC(ON1C(=O)CCC1=O)=O>C1COCC1.O.C(Cl)Cl>[NH:1]([C:6]([O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)=[O:7])[CH2:2][C:3]([NH:31][C@H:32]([C:41]([NH:43][CH2:44][C:45]([OH:47])=[O:46])=[O:42])[CH2:33][C:34](=[O:40])[O:35][C:36]([CH3:37])([CH3:38])[CH3:39])=[O:5]

Participants

9

Reactant 5

HCID 10868DicyclohexylcarbodiimideHCID 14349BenzyloxycarbonylglycineHCID 76177Z-Gly-OSuHCID 516892Sodium BicarbonateHCID 14375965HCID 14375965, compound

Product 1

HCID 131720724HCID 131720724, compoundYield 93%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

A mixture of Cbz-Gly-OH (6280 mg, 30 mmol), SuOH (3450 mg, 30 mmol) and DCC (6190 mg, 30 mmol) in dry THF (50 mL) was place d in refrigerator at 5° C. for 11 hours. The precipitated urea was filtered off and the filtrate was evaporated. The evaporated residue was triturated from CHCl3/hexanes and the N-hydroxysuccinimide ester was dried in vacuo (8140 mg, 89%). To a solution of H-Asp(OBut)-Gly-OH (2020 mg, 8.2 mmol) and NaHCO3 (1380 mg, 16.4 mmol) in water (40 mL) was added a solution of Cbz-Gly-OSu (2520 mg, 8.2 mmol) in THF (40 mL) and the mixture was stirred at r.t. for two hours. The mixture was added CH2Cl2 (200 mL) and washed with 1N HCl (200 mL) and water (200 mL). The organic layer was evaporated to give the titled compound (3330 mg, 93%): 1H NMR (300 MHz, DMSO-d6) δ 12.552 (s, 1H), 8.169 (m, 2H), 7.450 (t, J=6.0 Hz, 1H), 7.386 (s, 5H), 5.018 (s, 2H), 4.650 (qd, J=7.3, 2.4 Hz, 1H), 3.8-3.5 (m, 4H), 2.641 (dd, J=15.9, 5.4 Hz, 1H), 2.424 (dd, J=15.9, 8.1 Hz, 1H), 1.363 (s, 9H); 13C NMR (300 MHz, DMSO-d6) δ 171.0, 170.7, 169.2, 169.0, 156.5, 137.0, 128.4, 127.8 (2C), 80.2, 65.5, 49.2, 43.5, 40.8, 37.7, 27.7.

Workup

  1. filtrationThe precipitated urea was filtered off
  2. customthe filtrate was evaporated
  3. customThe evaporated residue was triturated from CHCl3/hexanes
  4. dry with materialthe N-hydroxysuccinimide ester was dried in vacuo (8140 mg, 89%)
  5. washwashed with 1N HCl (200 mL) and water (200 mL)
  6. customThe organic layer was evaporated

Sources & evidence

ORD record
ord-0ec39338242343e5870aa3a59b7ea140
Source dataset
uspto-grants-1998_06
Patent number
US05770380

Reaction notes

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