Tetrahydrofuran → HCID 71520078, compound

HRID 633664Notes

Reaction equation

HRID 633664 reaction equation
C1COCC1.[CH3:6][O:7][C:8]1[C@:15]2([CH2:18][CH:19]=[C:20]([CH3:22])[CH3:21])[C:16](=[O:17])[C@@H:11]([C@:12]([CH3:42])([CH2:28][CH2:29][CH2:30][C:31]([CH3:41])([O:33][Si:34]([CH2:39][CH3:40])([CH2:37][CH3:38])[CH2:35][CH3:36])[CH3:32])[C@@H:13]([CH2:23][CH:24]=[C:25]([CH3:27])[CH3:26])[CH2:14]2)[C:10](=[O:43])[C:9]=1[Si:44]([CH3:47])([CH3:46])[CH3:45].[Li]N1C(C)(C)CCCC1(C)C.[C:59](Cl)(=[O:63])[CH:60]([CH3:62])[CH3:61]>CCOC(C)=O.CCCCCC>[C:59]([C@:11]12[C:16](=[O:17])[C@:15]([CH2:18][CH:19]=[C:20]([CH3:21])[CH3:22])([CH2:14][C@H:13]([CH2:23][CH:24]=[C:25]([CH3:27])[CH3:26])[C@@:12]1([CH3:42])[CH2:28][CH2:29][CH2:30][C:31]([CH3:41])([O:33][Si:34]([CH2:35][CH3:36])([CH2:37][CH3:38])[CH2:39][CH3:40])[CH3:32])[C:8]([O:7][CH3:6])=[C:9]([Si:44]([CH3:47])([CH3:46])[CH3:45])[C:10]2=[O:43])(=[O:63])[CH:60]([CH3:62])[CH3:61]

Participants

7

Reactant 4

HCID 8028Tetrahydrofuran2×HCID 62325Isobutyryl chlorideHCID 71520077HCID 71520077, compound2×HCID 178418821HCID 178418821, compound

Product 1

HCID 71520078HCID 71520078, compoundYield 24%

Reagents, catalysts & solvents 2

HCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

A THF (0.5 mL) solution of 45 (7.0 mg, 11 μmol, 1 equiv.) was cooled to −78° C. in a 10-mL test tube, and a freshly prepared THF solution of lithium tetramethylpiperidide (0.50 M, 113 μL, 57 μmol, 5 equiv.) was added dropwise. The resulting yellow-orange solution was stirred at −78° C. for 10 min and at 0° C. for 10 min. The solution was then cooled to −78° C., and isobutyryl chloride (6.0 μL, 57 μmol, 5 equiv.) was added. The resulting yellow solution was stirred at −78° C. for 50 min, was slowly warmed to 0° C. over 50 min, and subsequently quenched with saturated aqueous NaHCO3. The mixture was warmed to room temperature and extracted thrice with EtOAc. The organic extracts were combined, washed with H2O and brine, dried over Na2SO4, filtered, and concentrated in vacuo to a yellow residue. Preparatory thin-layer chromatography (3×98:2 hexane:EtOAc) afforded 1.8 mg (2.6 μmol, 24% yield) of 46 as a colorless residue along with 1.7 mg (2.8 μmol, 25% recovery) of 45. TLC Rf 0.47 (95:5 hexane:EtOAc). 1H-NMR (600 MHz; CDCl3): δ 5.00-4.96 (m, 2H), 3.90 (s, 3H), 2.55 (dd, J=14.6, 6.4 Hz, 1H), 2.41 (dd, J=14.5, 7.7 Hz, 1H), 2.08 (d, J=15.0 Hz, 1H), 1.97 (septet, J=6.5 Hz, 1H), 1.92-1.85 (m, 2H), 1.79-1.72 (m, 1H), 1.68 (s, 3H), 1.66 (s, 3H), 1.57-1.56 (m, 3H), 1.55-1.53 (m, 3H), 1.50-1.42 (m, 2H), 1.39-1.31 (m, 3H), 1.30-1.24 (m, 2H), 1.17 (s, 3H), 1.17 (s, 3H), 1.13 (d, J=6.5 Hz, 3H), 1.02 (d, J=6.5 Hz, 3H), 0.98 (s, 3H), 0.92 (t, J=7.9 Hz, 9H), 0.54 (q, J=7.9 Hz, 6H), 0.26 (s, 9H). HRMS-ESI (m/z): [M+Na]+ calculated for C40H70O5Si2, 709.4654. found, 709.4626.

Workup

  1. temperatureThe solution was then cooled to −78° C.
  2. stirringThe resulting yellow solution was stirred at −78° C. for 50 min
  3. temperaturewas slowly warmed to 0° C. over 50 min
  4. customsubsequently quenched with saturated aqueous NaHCO3
  5. temperatureThe mixture was warmed to room temperature
  6. extractionextracted thrice with EtOAc
  7. washwashed with H2O and brine
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo to a yellow residue

Sources & evidence

ORD record
ord-f4827c153cc94f78843a58d871301d5f
Source dataset
uspto-grants-2016_04
Patent number
US09321713B2

Reaction notes

Loading…