Diethyl Ether → HCID 86701308, compound

HRID 1627041Notes

Reaction equation

HRID 1627041 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.[CH3:37][Mg]Br.C(OCC)C>C(Cl)Cl>[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 3

HCID 3283Diethyl EtherHCID 86701309HCID 86701309, compoundHCID 178418573HCID 178418573, compound

Product 1

HCID 86701308HCID 86701308, compoundYield 47%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-70 °C

Procedure

To a solution of (S)-methyl 3-((2S,3R)-2,3-bis(benzyloxy)-4-oxobutoxy)-2-((tert-butoxycarbonyl)amino)propanoate (0.980 g, 1.95 mmol) in DCM (18.61 ml) at −78° C. was added a 3.0 M solution of methylmagnesium bromide in diethyl ether (Et2O) (1.30 ml, 3.91 mmol) and the reaction was stirred at −70° C. for 1 h, warmed slowly to −20° C. over 2 h, and then quenched at −20° C. with H2O. The organic layer was separated and the aqueous layer was extracted with EtOAc. The combined organic phases were washed with brine, dried over MgSO4, filtered, and the filtrate was concentrated and purified by flash chromatography (SiO2, hexanes/EtOAc gradient) to yield the title compound as a colorless oil (0.475 g, 47%): 1H NMR (400 MHz, CDCl3) δ 7.37-7.27 (m, 10H), 5.43 (d, J=8.6 Hz, 1H), 4.71 (d, J=14.0 Hz, 1H), 4.69 (d, J=14.4 Hz, 1H), 4.55 (dd, J=11.5, 2.6 Hz, 2H), 4.49-4.41 (m, 1H), 3.96-3.84 (m, 2H), 3.75 (dd, J=10.1, 5.0 Hz, 1H), 3.72 (s, 3H), 3.71-3.63 (m, 3H), 3.32-3.29 (m, 1H), 2.26 (d, J=6.3 Hz, 1H), 1.45 (s, 9H), 1.14 (d, J=6.4 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ 171.20, 155.58, 138.36, 138.21, 128.59, 128.53, 128.21, 128.07, 128.05, 127.89, 82.88, 80.16, 78.55, 74.94, 73.18, 71.71, 71.34, 67.04, 54.16, 52.58, 28.46, 20.30; ESIMS m/z 516.3 ([M−H]−).

Workup

  1. temperaturewarmed slowly to −20° C. over 2 h
  2. customquenched at −20° C. with H2O
  3. customThe organic layer was separated
  4. extractionthe aqueous layer was extracted with EtOAc
  5. washThe combined organic phases were washed with brine
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationthe filtrate was concentrated
  9. custompurified by flash chromatography (SiO2, hexanes/EtOAc gradient)

Sources & evidence

ORD record
ord-9c191709f3fb4bd8af6fa3768bc5cb8a
Source dataset
uspto-grants-2014_07
Patent number
US08785479B2

Reaction notes

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