2,6-Lutidine → HCID 67587214, compound

HRID 1416786Notes

Reaction equation

HRID 1416786 reaction equation
[CH2:1]([O:3][C:4]([C:6]1([C:37]([O:39][CH2:40][CH3:41])=[O:38])[O:10][C:9]2[CH:11]=[CH:12][C:13]([CH2:15][C@H:16]([N:18]([CH2:27][C@@H:28]([C:30]3[CH:35]=[CH:34][CH:33]=[C:32]([Cl:36])[CH:31]=3)[OH:29])[C:19]([O:21][CH2:22][C:23]([Cl:26])([Cl:25])[Cl:24])=[O:20])[CH3:17])=[CH:14][C:8]=2[O:7]1)=[O:5])[CH3:2].CC1C=CC=C(C)N=1.[Si:50](OS(C(F)(F)F)(=O)=O)([C:53]([CH3:56])([CH3:55])[CH3:54])([CH3:52])[CH3:51]>C(Cl)Cl>[CH2:40]([O:39][C:37]([C:6]1([C:4]([O:3][CH2:1][CH3:2])=[O:5])[O:10][C:9]2[CH:11]=[CH:12][C:13]([CH2:15][C@H:16]([N:18]([CH2:27][C@H:28]([O:29][Si:50]([C:53]([CH3:56])([CH3:55])[CH3:54])([CH3:52])[CH3:51])[C:30]3[CH:35]=[CH:34][CH:33]=[C:32]([Cl:36])[CH:31]=3)[C:19]([O:21][CH2:22][C:23]([Cl:25])([Cl:24])[Cl:26])=[O:20])[CH3:17])=[CH:14][C:8]=2[O:7]1)=[O:38])[CH3:41]

Participants

5

Reactant 3

HCID 79372,6-LutidineHCID 123564tert-Butyldimethylsilyl trifluoromethanesulphonateHCID 86754135HCID 86754135, compound

Product 1

HCID 67587214HCID 67587214, compoundYield 82%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-78 °C

Procedure

To a -78° C. solution of 3.75 g (5.47 mmol) (R,R)-5-{2-[[2-(3-chloro-phenyl)-2-hydroxy-ethyl]-(2,2,2-trichloro-ethoxycarbonyl)-amino]-propyl}-benzo[1,3]dioxole-2,2-dicarboxylic acid diethyl ester and 60 mL of CH2Cl2 was added 1.27 mL (1.17 g, 10.94 mmol) of 2,6-lutidene followed by 1.38 mL (1.59 g, 6.03 mmol) of TBSOTf. After stirring at -78° C. for 1.5 h, the reaction mixture was quenched with 50 mL sat. aq. NaHCO3 and warmed to room temperature. After extraction with 3×150 mL Et2O, the combined organics were washed with 1×200 mL sat. CuSO4, 1×200 mL brine, dried over MgSO4, filtered and evaporated to a cloudy white oil. Flash chromatography on silica gel, eluting with hexanes/EtOAc (8/1 to 4/1) gave 3.42 g (4.46 mmol, an 82% yield) of the title compound (Rf =0.31; 4/1 hexanes/EtOAc) as a gummy colorless solid; 1H NMR (300 MHz, CDCl3): δ-0.13-(-0.08) (m, 3H), 0.00-0.06 (m, 3H), 0.85-0.91 (m, 9H), 1.05 (d, J=6.7 Hz, 3H), 1.33 (t, J=7.1 Hz, 6H), 2.60-2.75 (m, 1H), 2.77-2.96 (m, 1H), 3.00-3.31 (m, 2H), 3.77-4.00 (m, 1H), 4.35 (q, J=7.1 Hz, 4H), 4.65-4.88 (m, 2H), 5.02-5.20 (m, 1H), 6.60-6.85 (m, 4H), 7.15-7.37 (m, 3H); MS (ES) m/z (relative intensity): 790 (M+ +Na, 100), 768 (M+ +H, 20).

Workup

  1. customthe reaction mixture was quenched with 50 mL sat. aq. NaHCO3
  2. temperaturewarmed to room temperature
  3. extractionAfter extraction with 3×150 mL Et2O
  4. washthe combined organics were washed with 1×200 mL sat. CuSO4, 1×200 mL brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. customevaporated to a cloudy white oil
  8. washFlash chromatography on silica gel, eluting with hexanes/EtOAc (8/1 to 4/1)
  9. customgave 3.42 g (4.46 mmol

Sources & evidence

ORD record
ord-23005d13ff724ed98838e37e81c503b2
Source dataset
uspto-grants-1999_06
Patent number
US05914339

Reaction notes

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