Proton sponge → HCID 67145355, compound

HRID 2109787Notes

Reaction equation

HRID 2109787 reaction equation
F[B-](F)(F)F.C[O+:7]([CH3:9])[CH3:8].CN(C1C2C(N(C)C)=CC=CC=2C=CC=1)C.[C:26]([O:32][CH2:33][C@@H:34]([C:48]([O:50][C:51]([CH3:54])([CH3:53])[CH3:52])=[O:49])[C@@H:35]([C:38]1[CH:43]=[CH:42][C:41]([C:44]([F:47])([F:46])[F:45])=[CH:40][CH:39]=1)CO)(=[O:31])[C:27]([CH3:30])([CH3:29])[CH3:28]>C(Cl)Cl>[C:26]([O:32][CH2:33][C@@H:34]([C:48]([O:50][C:51]([CH3:54])([CH3:53])[CH3:52])=[O:49])[C@@H:35]([C:38]1[CH:39]=[CH:40][C:41]([C:44]([F:47])([F:46])[F:45])=[CH:42][CH:43]=1)[CH2:8][O:7][CH3:9])(=[O:31])[C:27]([CH3:28])([CH3:30])[CH3:29]

Participants

5

Reactant 3

HCID 88675Proton spongeHCID 2735153Oxonium, trimethyl-, tetrafluoroborate(1-) (1:1)HCID 67145335HCID 67145335, compound

Product 1

HCID 67145355HCID 67145355, compoundYield 62.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Trimethyloxonium tetrafluoroborate (2.3 g, 16 mmol) was taken up in 10 mL of CH2Cl2. Proton sponge (3.3 g, 16 mmol) and (2S,3S)-2-(tert-butoxycarbonyl)-4-hydroxy-3-(4-(trifluoromethyl)phenyl)butyl pivalate (2.25 g, 5.2 mmol) were added to the mixture in 15 mL of CH2Cl2. The mixture was shielded from light and stirred for 3 hours. The mixture was carefully quenched with 70 mL of 10% aq HCl and extracted three times with 100 mL of CH2Cl2. The combined organic extracts were dried over MgSO4. Filtration and concentration under reduced pressure, followed by flash chromatography on silica gel (5% to 25% EtOAc/hexanes) afforded (2S,3S)-2-(tert-butoxycarbonyl)-4-methoxy-3-(4-(trifluoromethyl)phenyl)butyl pivalate (1.4 g, 60% yield) as a white solid. 1H NMR (400 MHz, CDCl3) δ ppm 7.58 (d, J=8.02 Hz, 2H) 7.34 (d, J=8.02 Hz, 2H) 4.42-4.32 (m, 2H) 4.15-4.00 (m, 2H) 3.73-3.63 (m, 2H) 3.34 (s, 3H) 1.35 (s, 9H) 1.19 (s, 9H).

Workup

  1. customThe mixture was carefully quenched with 70 mL of 10% aq HCl
  2. extractionextracted three times with 100 mL of CH2Cl2
  3. dry with materialThe combined organic extracts were dried over MgSO4
  4. filtrationFiltration and concentration under reduced pressure

Sources & evidence

ORD record
ord-8f3db8035e6d43e2b7978d2b6988bbd7
Source dataset
uspto-grants-2009_04
Patent number
US07514566B2

Reaction notes

Loading…