Methyl L-phenylalaninate hydrochloride → HCID 15228291, compound

HRID 553076Notes

Reaction equation

HRID 553076 reaction equation
[CH2:1]([O:8][C:9](=[O:37])[C@@H:10]1[CH2:14]CC[N:11]1[C:15](=[O:36])[CH2:16][CH2:17][C:18](=[O:35])[C@@H:19]([NH:27][C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)C1C=CC=CC=1.[C:38]1(C[C@H](NC(OC(C)(C)C)=O)C(=O)CCC(O)=O)[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1.Cl.COC(=O)[C@H](CC1C=CC=CC=1)N.O.ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C.CCN(C(C)C)C(C)C>CN(C=O)C.C(Cl)Cl>[CH3:1][O:8][C:9](=[O:37])[C@H:10]([CH2:14][C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1)[NH:11][C:15](=[O:36])[CH2:16][CH2:17][C:18](=[O:35])[C@@H:19]([NH:27][C:28]([O:30][C:31]([CH3:33])([CH3:32])[CH3:34])=[O:29])[CH2:20][C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1

Participants

8

Reactant 6

HCID 75736Methyl L-phenylalaninate hydrochlorideHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 15109748HCID 15109748, compoundHCID 57956925HCID 57956925, compound

Product 1

HCID 15228291HCID 15228291, compoundYield 95%

Reagents, catalysts & solvents 1

HCID 22350042dichloromethane N,N-dimethylformamideSolvent

Procedure

The experimental procedure employed for the synthesis of (5S)-6-phenyl-5-[(tert-butyloxycarbonyl)-amino]-4-oxo-hexanoyl-L-proline benzyl ester was followed using the free acid compound 9 (98 mg, 0.3054 mmol, 1.0 eq.), L-phenylalanine methyl ester hydrochloride (55 mg, 0.3054 mmol, 1.0 eq.), 1-Hydroxybenzotriazole hydrate (HOBt) (42 mg, 0.3054 mmol, 1.0 eq.), N-ethyl-N′-(dimethylaminopropyl)-carbodiimide hydrochloride (EDC.HCl) (59 mg, 0.3054 mmol, 1.0 eq.), iPr2NEt (0.11 mL, 0.6110 mmol, 2.0 eq.) and dry DMF/CH2Cl2 (2:8 ratio)(5 mL). Work-up as usual and column chromatography on silica gel elution with 33% EtOAc-hexane afforded the (5S)-6-phenyl-5-[(tert-butyloxycarbonyl)-amino]-4-oxo-hexanoyl-L-phenylalanine methyl ester (NACE 119) as a pale viscous oil (0.140 g, 95%); Rf 0.35 (40% EtOAc-hexane); IR (liquid film) ν 1645 (CO) and 3170 (broad, NH) cm−1; 1H NMR (400 MHz, CDCl3) δH 1.39 (9H, s, (CH3)3), 2.44 (2H, t, J=6.2 Hz, —CH2CO), 2.77 (2H, m, —CH2CO), 2.91 (1H, dd, J=6.6 and 13.2 Hz, —CHαPh), 3.00-3.15 (3H, m, —CHβPh and —CH2Ph), 3.71 (3H, s, OCH3), 4.49 (1H, m, —CH—), 4.84 (1H, m, —CH—), 5.07 (1H, d, J=7.0 Hz, —NH), 6.03 (1H, d, J=7.7 Hz, —NH) and 7.08-7.58 (10H, m, Ar—H); 13C NMR (100 MHz, CDCl3) δC 28.2, 29.3, 29.4, 37.8 (2C), 52.2, 53.2, 60.3, 64.8, 126.9 (2C), 127.0, 127.1, 128.4, 128.5, 128.6, 129.2, 129.3, 129.5, 135.8, 136.4, 158.3, 171.9, 172.0 and 206.7; EI-MS m/z calcd for C27H34N2O6 (M+) 482.2417, found 482 (M+).

Workup

  1. washon silica gel elution with 33% EtOAc-hexane

Sources & evidence

ORD record
ord-f89ad805aa12469b87dbf85f11a5a1dc
Source dataset
uspto-grants-2011_05
Patent number
US07951834B2

Reaction notes

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