HCID 11407294, compound → HCID 11480063, compound

HRID 2252482Notes

Reaction equation

HRID 2252482 reaction equation
[Si:1]([O:8][C@H:9]([C@@H:14]([CH3:27])[CH2:15][C@H:16]([CH2:18][O:19][Si:20]([C:23]([CH3:26])([CH3:25])[CH3:24])([CH3:22])[CH3:21])[CH3:17])[C@@H:10]([CH3:13])[C:11]#[CH:12])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[Li]CCCC.[Si:33]([O:40][C@H:41]([C@H:49]([CH3:73])/[CH:50]=[CH:51]/[CH2:52][O:53][C:54]([C:67]1[CH:72]=[CH:71][CH:70]=[CH:69][CH:68]=1)([C:61]1[CH:66]=[CH:65][CH:64]=[CH:63][CH:62]=1)[C:55]1[CH:60]=[CH:59][CH:58]=[CH:57][CH:56]=1)[CH2:42][C:43](N(OC)C)=[O:44])([C:36]([CH3:39])([CH3:38])[CH3:37])([CH3:35])[CH3:34]>C1COCC1>[Si:33]([O:40][C@@H:41]([CH2:42][C:43](=[O:44])[C:12]#[C:11][C@H:10]([CH3:13])[C@H:9]([O:8][Si:1]([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2])[C@@H:14]([CH3:27])[CH2:15][C@@H:16]([CH3:17])[CH2:18][O:19][Si:20]([C:23]([CH3:24])([CH3:25])[CH3:26])([CH3:22])[CH3:21])[C@H:49]([CH3:73])/[CH:50]=[CH:51]/[CH2:52][O:53][C:54]([C:67]1[CH:72]=[CH:71][CH:70]=[CH:69][CH:68]=1)([C:61]1[CH:66]=[CH:65][CH:64]=[CH:63][CH:62]=1)[C:55]1[CH:56]=[CH:57][CH:58]=[CH:59][CH:60]=1)([C:36]([CH3:39])([CH3:37])[CH3:38])([CH3:35])[CH3:34]

Participants

5

Reactant 3

HCID 11407294HCID 11407294, compoundHCID 11786472HCID 11786472, compoundHCID 178418339Butyllithium

Product 1

HCID 11480063HCID 11480063, compoundYield 104.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

Alkyne 29 (4.12 g, 10.0 mmol) was dissolved in THF (100 mL) and cooled to −78° C. n-BuLi (6.25 mL, 1.6 M hexane solution) was added slowly. After 5 min, the mixture was warmed to 0° C. and stirred for 30 min. The mixture was then cooled to −78° C. and amide 15 (6.47 g, 11.3 mmol) in THF (5 mL) was added slowly. After 5 min, the solution was warmed to 0° C. and stirred for 30 min. The reaction was quenched with saturated aqueous NH4Cl and the mixture was partitioned in a separatory funnel. The aqueous phase was extracted with Et2O (3×20 mL). The combined organic extracts were washed with brine and dried over MgSO4. Filtration and concentration under reduced pressure, followed by flash chromatography on silica gel (hexane/EtOAc 19:1), afforded the ynone 32 (9.70 g, 93%) as a pale yellow oil: IR (CHCl3) 2955, 2928, 2856, 2209, 1676, 1471, 1462, 1252, 1085, 836, 774 cm−1; 1H NMR (300 MHz, CDCl3) ε7.56 m, 6H), 7.36 (m, 9H), 5.80 (dd, J=15.6, 7.1 Hz, 1H), 5.69 (dt, J=15.7, 4.8 Hz, 1H), 4.37 (m, 1H), 3.69 (d, J=4.7 Hz, 2H), 3.61 (m, 1H), 3.58 (dd, J=9.7, 5.0 Hz, 1H), 3.43 (dd, J=9.7, 6.5 Hz, 1H), 2.87 (m, 1H), 2.73 (m, 1H), 2.46 (m, 1H), 1.88 (m, 1H), 1.76 (m, 1H), 1.59 (m, 1H), 1.31 (d, J=7.1 Hz, 3H), 1.15 (d, J=6.8 Hz, 3H), 1.05 (m, 1H), 1.00 (m, 3H), 0.194 (s, 3H), 0.190 (s, 3H), 0.17 (s, 3H), 0.15 (s, 3H), 0.14 (s, 6H); 13C NMR (75 MHz, CDCl3) δ 186.1, 144.2, 132.9, 128.6, 127.7, 126.9, 96.8, 86.8, 83.1, 71.5, 68.0, 64.9, 50.0, 42.3, 38.1, 34.4, 33.2, 32.1, 26.01, 25.96, 25.85, 18.3, 18.0, 17.9, 17.2, 15.5, 15.4, −3.8, −4.1, −4.6, −4.7, −5.4; LRMS (ESI) 947.5 [M+Na]+, 562.3, 243.1; HRMS (ESI) calcd for C56H88O5Si3Na 947.5837 [M+Na]+, found 947.5875; [α]20D−12.0 (c 0.54, CHCl3).

Workup

  1. additionwas added slowly
  2. temperatureThe mixture was then cooled to −78° C.
  3. waitAfter 5 min
  4. temperaturethe solution was warmed to 0° C.
  5. stirringstirred for 30 min
  6. customThe reaction was quenched with saturated aqueous NH4Cl
  7. customthe mixture was partitioned in a separatory funnel
  8. extractionThe aqueous phase was extracted with Et2O (3×20 mL)
  9. washThe combined organic extracts were washed with brine
  10. dry with materialdried over MgSO4
  11. filtrationFiltration and concentration under reduced pressure

Sources & evidence

ORD record
ord-e9a1dd8b17bc4963846fc1156c1e935d
Source dataset
uspto-grants-2008_01
Patent number
US07321046B2

Reaction notes

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