Dichloromethane → HCID 86701318, compound

HRID 2283011Notes

Reaction equation

HRID 2283011 reaction equation
[CH2:1]([O:8][C@H:9]([C@@H:26]([O:29][CH2:30][C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)[CH:27]=[O:28])[CH2:10][O:11][CH2:12][C@H:13]([NH:18][C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[C:14]([O:16][CH3:17])=[O:15])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:37](Cl)Cl>C1COCC1.C(O[Ti](OC(C)C)(OC(C)C)C)(C)C>[CH2:1]([O:8][C@H:9]([C@@H:26]([O:29][CH2:30][C:31]1[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=1)[C@@H:27]([OH:28])[CH3:37])[CH2:10][O:11][CH2:12][C@H:13]([NH:18][C:19]([O:21][C:22]([CH3:24])([CH3:25])[CH3:23])=[O:20])[C:14]([O:16][CH3:17])=[O:15])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 2

HCID 6344DichloromethaneHCID 86701309HCID 86701309, compound

Product 1

HCID 86701318HCID 86701318, compoundYield 59%

Reagents, catalysts & solvents 2

HCID 178460661HCID 178460661, compoundCatalystHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a solution of (S)-methyl 3-((2S,3R)-2,3-bis(benzyloxy)-4-oxobutoxy)-2-((tert-butoxycarbonyl)amino)propanoate (7.55 g, 15.05 mmol) in DCM (30 ml) and THF (30 ml) at −78° C. was added triisopropoxy(methyl)titanium, 1.0 M in THF (31.6 ml, 31.6 mmol) and the reaction was stirred at −78° C. for 2 h, warmed to −20° C., and stored at −20° C. overnight. The reaction was warmed to 0° C., stirred for 4 h between 0° C. and −10° C., and then quenched at this temperature with saturated aqueous NH4Cl. The reaction mixture was extracted with EtOAc, and the combined extracts were washed with brine, dried over MgSO4, filtered, and concentrated. The crude residue was purified by flash chromatography (SiO2, hexanes/EtOAc) to yield the title compound as a colorless oil (4.59 g, 59%, diastereomer selectivity=6:1): 1H NMR (400 MHz, CDCl3) δ 7.45-7.14 (m, 11H), 5.45 (d, J=8.8 Hz, 1H), 4.67 (d, J=11.6 Hz, 1H), 4.61-4.51 (m, 3H), 4.50-4.41 (m, 1H), 3.90 (dd, J=9.4, 3.0 Hz, 1H), 3.84-3.78 (m, 1H), 3.74-3.61 (m, 6H), 3.31 (dd, J=6.8, 4.0 Hz, 1H), 2.85 (d, J=4.5 Hz, 1H), 1.45 (s, 9H), 1.20 (d, J=6.2 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ 171.04, 155.45, 137.99, 137.76, 128.51, 128.44, 128.12, 128.00, 127.97, 127.87, 81.43, 80.05, 77.91, 73.55, 72.88, 71.60, 70.91, 67.53, 54.00, 52.47, 28.34, 19.89; ESIMS m/z 540.6 ([M+Na]+).

Workup

  1. temperaturewarmed to −20° C.
  2. waitstored at −20° C. overnight
  3. temperatureThe reaction was warmed to 0° C.
  4. stirringstirred for 4 h between 0° C. and −10° C.
  5. customquenched at this temperature with saturated aqueous NH4Cl
  6. extractionThe reaction mixture was extracted with EtOAc
  7. washthe combined extracts were washed with brine
  8. dry with materialdried over MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe crude residue was purified by flash chromatography (SiO2, hexanes/EtOAc)

Sources & evidence

ORD record
ord-b50c117c86fa4e9b86e20587dcb7ea67
Source dataset
uspto-grants-2015_09
Patent number
US09144239B2

Reaction notes

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