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

HRID 1633845Notes

Reaction equation

HRID 1633845 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:31](O)=[O:32])[CH3:30])=[O:27])[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.C1C=CC2N(O)N=NC=2C=1.O.C1CCC(N=C=NC2CCCCC2)CC1>CN(C=O)C>[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:31](=[O:32])[C@@H:29]([CH3:30])[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

6

Reactant 4

HCID 10868DicyclohexylcarbodiimideHCID 70832N-Cbz-d-alanineHCID 27960291-Hydroxybenzotriazole hydrateHCID 117912751,1-Dimethylethyl 4-fluoro-3-[(methylamino)methyl]benzoate

Product 1

HCID 131723729Tert-butyl (r)-4-fluoro-3-[[[n-(benzyloxycarbonyl)-alaninyl]methylamino]methyl]benzoateYield 73.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of tert-butyl 4-fluoro-3-(methylaminomethyl)benzoate (2.42 g, 10.1 mmole) in DMF (75 mL) was added N-(benzyloxycarbonyl)-D-alanine (2.45 g, 11 mmole) and HOBt H2O (1.5 g, 11 mmole), followed by DCC (2.4 g, 11.6 mmole). The reaction was stirred for 16 h then was concentrated to dryness. Purification by flash chromatography on silica gel (30% EtOAc/hexanes) gave the title compound (3.29 g, 73%) as a clear oil: 1H NMR (300 MHz, CDCl3) mixture of amide rotamers δ 7.90-7.95 (m, 1 H), 7.81 (dd, 1 H), 7.31-7.32 (m, 5 H), 7.08 (t, 1 H), 5.72 & 5.83 (2 d, J=7.8 Hz, 1 H), 5.11 (s, 2 H), 4.89 (d, J=15.3 Hz, 1 H), 4.72-4.77 (m, 1 H), 4.47 (d, J=15.3 Hz 2.92 & 3.05 (2s, 3 H), 1.56(s, 9 H), 1.37 & 1.40(2 d, J =6.8Hz, 3 H).

Workup

  1. concentrationthen was concentrated to dryness
  2. customPurification by flash chromatography on silica gel (30% EtOAc/hexanes)

Sources & evidence

ORD record
ord-cd94e6ceba834d369aee5c0adf20e992
Source dataset
uspto-grants-2003_01
Patent number
US06503903B1

Reaction notes

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