Citric Acid → HCID 86635225, compound

HRID 476308Notes

Reaction equation

HRID 476308 reaction equation
[C:1]([O:5][C:6]([CH2:8][CH2:9][C@@H:10]([CH2:14][CH3:15])[C:11]([OH:13])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].[NH2:16][C@H:17]([C:25]([O:27][CH3:28])=[O:26])[CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.Cl.CCN=C=NCCCN(C)C.Cl.CCN(C(C)C)C(C)C.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C(Cl)Cl.CCOC(C)=O>[C:1]([O:5][C:6]([CH2:8][CH2:9][C@@H:10]([CH2:14][CH3:15])[C:11]([NH:16][C@@H:17]([CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[C:25]([O:27][CH3:28])=[O:26])=[O:13])=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

8

Reactant 5

HCID 311Citric AcidHCID 75736Methyl L-phenylalaninate hydrochlorideHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 86635226HCID 86635226, compound

Product 1

HCID 86635225HCID 86635225, compoundYield 83%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

Compound 4 (139 mg, 0.6 mmol) was dissolved in dry CH2Cl2 (6 mL) and treated with L-Phe-OMe.HCl (142 mg, 0.66 mmol), EDCI.HCl (138 mg, 0.72 mmol), DIEA (128 μL, 0.72 mmol). The reaction mixture was stirred for 24 h, diluted with EtOAc, acidified with 10% citric acid and extracted with EtOAc (3×). The combined organic layers were washed with saturated NaHCO3 and brine, dried (MgSO4) and concentrated. The crude residue was purified via column chromatography eluting with EtOAc/hexane to afford pure product 5 (188 mg, 80%) as a white solid. An analytical sample was purified by recrystallization (hexanes/EtOAc): m.p. 119.5-121° C. TLC Rf=0.60 (EtOAc/hexanes, v/v, 1:1). 1H NMR (500 MHz, CDCl3) δ 7.32-7.23 (m, 3H), 7.17-7.15 (m, 2H), 6.36 (bd, J=6.6 Hz, 1H), 4.96-4.89 (m, 1H), 4.54 (bs, 1H), 3.72 (s, 3H), 3.18, 3.07 (AB of ABX, JAB=13.9 Hz, JAX=6.0 Hz, JBX=7.2 Hz, 2H), 3.00-2.84 (m, 2H), 2.08-1.98 (m, 1H), 1.73-1.49 (m, 3H), 1.44 (s, 9H), 1.47-1.36 (m, 1H), 0.85 (t, J=7.5 Hz, 3H); 13C NMR (75 MHz, CDCl3) δ 175.23, 172.47, 156.43, 136.40, 129.38, 128.79, 127.28, 79.42, 53.16, 52.46, 46.46, 38.72, 38.18, 33.16, 28.61, 26.21, 12.04; HRMS m/z (ESI): calc. for C21H32N2O5Na [M+Na]+415.2204, found 415.2199. Optical rotation: [α]rtD+14.9 (c 1.06, CHCl3). In addition, N-Boc γ-lactam (7.6 mg, 6%) was isolated via column chromatography eluting with EtOAc/hexane.

Workup

  1. extractionextracted with EtOAc (3×)
  2. washThe combined organic layers were washed with saturated NaHCO3 and brine
  3. dry with materialdried (MgSO4)
  4. concentrationconcentrated
  5. customThe crude residue was purified via column chromatography
  6. washeluting with EtOAc/hexane

Sources & evidence

ORD record
ord-4c3ff46a0015472eb29b094ab43c1f88
Source dataset
uspto-grants-2014_01
Patent number
US08637696B2

Reaction notes

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