Triethylamine → (S)-3-(3'-chloro-biphenyl-4-yl)-2-((S)-1-ethoxycarbonyl-ethylamino)-propionic acid benzyl ester

HRID 331672Notes

Reaction equation

HRID 331672 reaction equation
[CH2:1]([O:8][C:9](=[O:26])[C@@H:10]([NH2:25])[CH2:11][C:12]1[CH:17]=[CH:16][C:15]([C:18]2[CH:23]=[CH:22][CH:21]=[C:20]([Cl:24])[CH:19]=2)=[CH:14][CH:13]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)CC)C.FC(F)(F)S(O[C@H:40]([CH3:46])[C:41]([O:43][CH2:44][CH3:45])=[O:42])(=O)=O>ClCCl>[CH2:1]([O:8][C:9](=[O:26])[C@@H:10]([NH:25][C@H:40]([C:41]([O:43][CH2:44][CH3:45])=[O:42])[CH3:46])[CH2:11][C:12]1[CH:17]=[CH:16][C:15]([C:18]2[CH:23]=[CH:22][CH:21]=[C:20]([Cl:24])[CH:19]=2)=[CH:14][CH:13]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 8471Triethylamine2×HCID 10999437Ethyl (R)-2-(trifluoromethylsulfonyloxy)propionate2×HCID 58280537(S)-2-amino-3-(3'-chloro-biphenyl-4-yl)-propionic acid benzyl ester

Product 1

HCID 58280560(S)-3-(3'-chloro-biphenyl-4-yl)-2-((S)-1-ethoxycarbonyl-ethylamino)-propionic acid benzyl esterYield 91.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (S)-2-amino-3-(3′-chloro-biphenyl-4-yl)-propionic acid benzyl ester (10.0 g, 24.9 mmol) in dichloromethane (100 mL) was added triethylamine (10.4 mL, 74.6 mmol) at 0° C. After stirred for 10 min, ethyl (R)-2-(trifluoromethylsulfonyloxy)propionate (9.3 mL, 49.5 mmol) was added at room temperature and stirred for 1 hour. Additional triethylamine (10.4 mL, 74.6 mmol) and ethyl (R)-2-(trifluoromethylsulfonyloxy)propionate (9.3 mL, 49.5 mmol) were added at room temperature and stirred for additional 2 hours. The reaction mixture was washed with H2O and the organic layer was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (EtOAc/heptane) to give (S)-3-(3′-chloro-biphenyl-4-yl)-2-((S)-1-ethoxycarbonyl-ethylamino)-propionic acid benzyl ester (10.6 g). 1H NMR (400 MHz, CDCl3) δ 1.21 (t, 3H, J=7.3 Hz), 1.27 (d, 3H, J=6.8 Hz), 1.89 (bs, 1H), 2.95-3.07 (m, 2H), 3.38 (dd, 1H, J=6.8, 14.8 Hz), 3.69 (dd, 1H, J=7.1, 7.1 Hz), 4.06-4.17 (m, 2H), 5.06 (d, 1H, J=12.1 Hz), 5.12 (d, 1H, J=12.1 Hz), 7.20-7.25 (m, 4H), 7.28-7.34 (m, 4H), 7.35 (dd, 1H, J=7.6, 7.6 Hz), 7.41-7.46 (m, 3H), 7.53 (dd, 1H, J=1.5, 1.5 Hz); MS: m/z (MW) 466.

Workup

  1. stirringstirred for 1 hour
  2. stirringstirred for additional 2 hours
  3. washThe reaction mixture was washed with H2O
  4. concentrationthe organic layer was concentrated under reduced pressure
  5. customThe obtained residue was purified by silica gel column chromatography (EtOAc/heptane)

Sources & evidence

ORD record
ord-d07cd805fe85401682020977851d5ef5
Source dataset
uspto-grants-2014_11
Patent number
US08877786B2

Reaction notes

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