1-Hydroxybenzotriazole → Boc-(D)Phe-Pro-OBzl

HRID 726651Notes

Reaction equation

HRID 726651 reaction equation
[NH:1]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[C@@H:2]([C:10]([OH:12])=O)[CH2:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[NH:20]1[CH2:34][CH2:33][CH2:32][C@H:21]1[C:22]([O:24][CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)=[O:23].Cl.C1C=CC2N(O)N=NC=2C=1.C(N(CC)C(C)C)(C)C.Cl.CN(C)CCCN=C=NCC>ClCCl.C(OCC)C>[NH:1]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[C@@H:2]([C:10]([N:20]1[CH2:34][CH2:33][CH2:32][C@H:21]1[C:22]([O:24][CH2:25][C:26]1[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=1)=[O:23])=[O:12])[CH2:3][C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=1

Participants

8

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 637610Boc-D-phenylalanineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 2733413Proline benzyl ester hydrochloride

Product 1

HCID 11155205Boc-(D)Phe-Pro-OBzlYield 92.5%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of Boc-D-Phe-OH (89.1 g, 336 mmol), Pro-OBn hydrochloride (81.2 g, 336 mmol), HOBT (50 g, 370 mmol) and N,N-diisopropylethylamine (176 mL, 1,008 mmol) at 0° C. in dichloromethane (600 mL) was added 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (71 g, 370 mmol). After stirring for 18 hours, the mixture was diluted with diethyl ether (1 L) and washed sequentially three times with 1N citric acid (250 mL), once with water (250 mL), three times with saturated aqueous sodium bicarbonate (250 mL) and once with saturated aqueous sodium chloride (250 mL). The organic phase was dried (Na2SO4), filtered, and concentrated in vacuo to yield 140 g (92.5%) of a pale yellow foam.

Workup

  1. washwashed sequentially three times with 1N citric acid (250 mL)
  2. dry with materialThe organic phase was dried (Na2SO4)
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-f26412b992b9433dbce3232676b3fda0
Source dataset
uspto-grants-1998_01
Patent number
US05710130

Reaction notes

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