Water → Tert-butyl (r)-4-fluoro-3-[[[n-(benzyloxycarbonyl)-norvalinyl]methylamino]methyl]benzoate

HRID 1884529Notes

Reaction equation

HRID 1884529 reaction equation
[F:1][C:2]1[CH:14]=[CH:13][C:5]([C:6]([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7])=[CH:4][C:3]=1[CH2:15][NH:16][CH3:17].[CH2:18]([O:25][C:26]([NH:28][C@@H:29]([C:33](O)=[O:34])[CH2:30][CH2:31][CH3:32])=[O:27])[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.C1C=CC2N(O)N=NC=2C=1.O.CCN(CC)CC.CCN=C=NCCCN(C)C.Cl>CN(C=O)C.C(Cl)Cl>[F:1][C:2]1[CH:14]=[CH:13][C:5]([C:6]([O:8][C:9]([CH3:11])([CH3:12])[CH3:10])=[O:7])=[CH:4][C:3]=1[CH2:15][NH:16][CH2:17][C:33](=[O:34])[C@@H:29]([CH2:30][CH2:31][CH3:32])[NH:28][C:26]([O:25][CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)=[O:27]

Participants

8

Reactant 6

HCID 962WaterHCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 10106192Z-D-Nva-OHHCID 117912751,1-Dimethylethyl 4-fluoro-3-[(methylamino)methyl]benzoate

Product 1

HCID 131723731Tert-butyl (r)-4-fluoro-3-[[[n-(benzyloxycarbonyl)-norvalinyl]methylamino]methyl]benzoateYield 97.3%

Reagents, catalysts & solvents 1

HCID 22350042dichloromethane N,N-dimethylformamideSolvent

Procedure

According to the procedure of Preparation 4 (c), except using tert-butyl 4-fluoro-3-(methylaminomethyl)benzoate (4.00 g, 16.7 mmole), N-(benzyloxycarbonyl)-D-norvaline (4.20 g, 16.7 mmole), HOBt.H2O (2.3 g, 17 mmole), Et3N (2.4 mL, 17.1 mmole), EDC.HCl (3.3 g, 17.2 mmole), and 1:1 DMF/CH2Cl2 (100 mL), the title compound (7.68 g, 97%) was prepared as a thick yellow oil following flash chromatography on silica gel (30% EtOAc/hexanes): 1H NMR (300 MHz, DMSO-d6) mixture of amide rotamers δ 7.81-7.92 (m, 1H), 7.70-7.80 (m, 1H), 7.52-7.65 (m, 1H), 7.25-7.38 (m, 5H), 4.62-5.08 (m, 3 H), 4.38-4.53 (m, 2H), 2.83 & 3.07(2s, 3H), 1.52-1.58 (m, 2H), 1.52 (s, 9H), 1.15-1.37 (m, 2H), 0.74 & 0.87 (2 t, 3H).

Sources & evidence

ORD record
ord-c47736c5afc34cbbac7c4722dad75401
Source dataset
uspto-grants-2004_07
Patent number
US06765005B2

Reaction notes

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