2,6-Lutidine → tert-Butyl (R)-2-[(trifluoromethylsulfonyl)oxy]propionate

HRID 388874Notes

Reaction equation

HRID 388874 reaction equation
[C:1]([O:5][C:6](=[O:10])[C@H:7](O)[CH3:8])([CH3:4])([CH3:3])[CH3:2].S(OS(C(F)(F)F)(=O)=O)(C(F)(F)F)(=O)=O.N1C(C)=CC=CC=1C.Cl.[CH2:35]([O:42][C:43](=[O:61])[C@@H:44]([NH2:60])[CH2:45][C:46]1[CH:51]=[CH:50][C:49]([C:52]2[CH:57]=[C:56]([Cl:58])[CH:55]=[CH:54][C:53]=2[Cl:59])=[CH:48][CH:47]=1)[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1.C(N(CC)CC)C.[F:69][C:70]([F:85])([F:84])[S:71]([O:74][C@H:75]([CH3:83])[C:76]([O:78][C:79]([CH3:82])([CH3:81])[CH3:80])=[O:77])(=[O:73])=[O:72]>C(Cl)Cl>[F:84][C:70]([F:69])([F:85])[S:71]([O:74][C@H:75]([CH3:83])[C:76]([O:78][C:79]([CH3:80])([CH3:81])[CH3:82])=[O:77])(=[O:72])=[O:73].[CH2:35]([O:42][C:43](=[O:61])[C@@H:44]([NH:60][C@H:7]([C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:10])[CH3:8])[CH2:45][C:46]1[CH:51]=[CH:50][C:49]([C:52]2[CH:57]=[C:56]([Cl:58])[CH:55]=[CH:54][C:53]=2[Cl:59])=[CH:48][CH:47]=1)[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1

Participants

9

Reactant 6

HCID 79372,6-LutidineHCID 8471Triethylamine2×HCID 67749Trifluoromethanesulfonic anhydrideHCID 10953655tert-butyl (2R)-2-hydroxypropanoateHCID 13563137tert-Butyl (R)-2-[(trifluoromethylsulfonyl)oxy]propionate2×HCID 67154151(S)-2-amino-3-(2',5'-dichloro-biphenyl-4-yl)-propionic acid benzyl ester hydrochloride

Product 2

HCID 13563137tert-Butyl (R)-2-[(trifluoromethylsulfonyl)oxy]propionateHCID 58280524(S)-2-((S)-1-tert-butoxycarbonyl-ethylamino)-3-(2',5'-dichloro-biphenyl-4-yl)-propionic acid benzyl ester

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Step 3′: t-Butyl (R)-2-(trifluoromethylsulfonyloxy)propionate was prepared from (R)-2-hydroxy-propionic acid tert-butyl ester (602 mg, 4.12 mmol), triflic anhydride (0.696 mL, 4.12 mmol) and 2,6-lutidine (0.480 mL, 4.12 mmol) in DCM (5 mL). To a suspension of ((S)-2-amino-3-(2′,5′-dichloro-biphenyl-4-yl)-propionic acid benzyl ester hydrochloride (600 mg, 1.38 mmol) in dichloromethane (10 mL) was added triethylamine (0.574 mL, 4.12 mmol) at 0° C. After stirred for 10 min, a half amount of the freshly prepared t-butyl (R)-2-(trifluoromethylsulfonyloxy)propionate was added at room temperature and stirred for 1 hour. Additional triethylamine (0.574 mL, 4.12 mmol) and the rest of t-butyl (R)-2-(trifluoromethylsulfonyloxy)propionate 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)-2-((S)-1-tert-butoxycarbonyl-ethylamino)-3-(2′,5′-dichloro-biphenyl-4-yl)-propionic acid benzyl ester (580 mg). 1H NMR (400 MHz, CDCl3) δ 1.24 (t, 3H, J=6.8 Hz), 1.41 (s, 9H), 3.00-3.07 (m, 2H), 3.26 (dd, 1H, J=7.1, 13.9 Hz), 3.70 (dd, 1H, J=7.1, 7.1 Hz), 5.09 (s, 2H), 7.20-7.42 (m, 12H); MS: m/z (MH+) 528.

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-2112aff76f9a4db29e44a6ef1678b1c6
Source dataset
uspto-grants-2013_02
Patent number
US08377978B2

Reaction notes

Loading…