Formaldehyde → 16-(Tert-butyldiphenylsilyloxy)hexadec-2-yn-1-ol

HRID 918989Notes

Reaction equation

HRID 918989 reaction equation
[Li]CCCC.[C:6]([Si:10]([O:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][C:37]#[CH:38])([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)([CH3:9])([CH3:8])[CH3:7].[CH2:39]=[O:40]>C1COCC1>[Si:10]([O:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][C:37]#[C:38][CH2:39][OH:40])([C:6]([CH3:9])([CH3:8])[CH3:7])([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1

Participants

5

Reactant 3

HCID 712FormaldehydeHCID 86665268Tert-butyl(pentadec-14-ynyloxy)diphenylsilaneHCID 178418339Butyllithium

Product 1

HCID 6742431016-(Tert-butyldiphenylsilyloxy)hexadec-2-yn-1-olYield 68%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-50 °C

Procedure

n-BuLi (2.5 M solution in hexanes, 1.29 g, 8 mL, 20.24 mmol) was added to a stirring, −40° C. solution of tert-butyl(pentadec-14-ynyloxy)diphenylsilane (8.5 g, 18.40 mmol) in THF (175 mL) under an argon atmosphere. After 30 min, the reaction mixture was gradually warmed over 3 h to −10° C., held at this temperature for 20 min, then re-cooled to −50° C. Then, a solution of paraformaldehyde (3.05 g, 92.2 mmol) in THF (30 mL) was cannulated into the stirring reaction mixture. After 30 min, the temperature was gradually warmed over 3 h to room temperature. Following 1 h at room temperature, the reaction mixture was quenched with sat. aq. NH4Cl (10 mL), diluted with ether (100 mL), and washed with water (2×75 mL). The combined aqueous washes were back-extracted with ether (2×50 mL). The combined All of the organic extracts were combined, dried over Na2SO4, and concentrated under reduced pressure. The residue was purified by SiO2 column chromatography using 5% EtOAc/hexanes as eluent to give 16-(tert-butyldiphenylsilyloxy)hexadec-2-yn-1-ol (6.12 g, 68%). TLC: 30% EtOAc/hexanes, Rf≈0.5; 1H NMR (CDCl3, 300 MHz) δ 7.70-7.74 (m, 4H), 7.34-7.44 (m, 6H), 4.3 (t, 2H, J=2.1 Hz), 3.65 (t, 2H, J=7.3 Hz), 2.12-2.17 (m, 2H), 1.20-1.61 (m, 22H), 1.04 (s, 9H).

Workup

  1. temperaturethe reaction mixture was gradually warmed over 3 h to −10° C.
  2. waitheld at this temperature for 20 min
  3. waitAfter 30 min
  4. temperaturethe temperature was gradually warmed over 3 h to room temperature
  5. waitFollowing 1 h at room temperature
  6. customthe reaction mixture was quenched with sat. aq. NH4Cl (10 mL)
  7. additiondiluted with ether (100 mL)
  8. washwashed with water (2×75 mL)
  9. extractionThe combined aqueous washes were back-extracted with ether (2×50 mL)
  10. dry with materialdried over Na2SO4
  11. concentrationconcentrated under reduced pressure
  12. customThe residue was purified by SiO2 column chromatography

Sources & evidence

ORD record
ord-31f532511eff4c3dab84e5ad31134a44
Source dataset
uspto-grants-2016_03
Patent number
US09272991B2

Reaction notes

Loading…