Formaldehyde → HCID 178484020, compound

HRID 1743797Notes

Reaction equation

HRID 1743797 reaction equation
CC1C=[C:12]2[O:14]C=1C[C@H](C(C)=C)CCC1C(=O)O[C@@H]([C@H]2C(C)=C)C=1.[C:24]([O:28][C:29](=[O:43])[N:30]([CH2:32][C@H:33]1[CH2:38][CH2:37][C@H:36]([CH:39]=[C:40](Br)Br)[CH2:35][CH2:34]1)[CH3:31])([CH3:27])([CH3:26])[CH3:25].[Li]CCCC.C=O>C1COCC1>[C:24]([O:28][C:29](=[O:43])[N:30]([CH2:32][C@H:33]1[CH2:38][CH2:37][C@H:36]([C:39]#[C:40][CH2:12][OH:14])[CH2:35][CH2:34]1)[CH3:31])([CH3:27])([CH3:26])[CH3:25]

Participants

6

Reactant 4

HCID 712FormaldehydeHCID 15760798(+)-Kallolide BHCID 178418339ButyllithiumHCID 178484007HCID 178484007, compound

Product 1

HCID 178484020HCID 178484020, compoundYield 54%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

The following reaction was performed in analogy to the reaction described in: Marshall, James A.; Bartley, Gary S.; Wallace, Eli M. Total Synthesis of the Pseudopterane (−)-Kallolide B, the Enantiomer of Natural (+)-Kallolide B. J. Org. Chem. (1996), 61(17), 5729–5735 and Baker, Raymond; Boyes, Alastair L.; Swain, Christopher J. Synthesis of talaromycins A, B, C, and E. J. Chem. Soc., Perkin Trans. 1 (1990), (5), 1415–21.). A solution of 32.9 g (80 mmol) of trans-[4-(2,2-Dibromo-vinyl)-cyclohexylmethyl]-methyl-carbamic acid tert-butyl ester in 640 ml THF was treated at −78° C. with 105 ml (168 mmol) of BuLi (ca 1.6 M in hexane). After 2 h at this temperature 24 g (800 mmol) of paraformaldehyde were added. The reaction mixture was warmed up to RT for 3 h and after 0.5 h at this temperature extracted with water/Et2O (3×). The organic phases were washed with aqueous 10% NaCl, dried over Na2SO4 and evaporated. Purification by flash-chromatography on silica gel (hexane/EtOAc 9:1 to 2:1) yielded 12.1 g (54%) of trans-[4-(3-Hydroxy-prop-1-ynyl)-cyclohexylmethyl]-methyl-carbamic acid tert-butyl ester, MS: 282 (MH+).

Workup

  1. customThe following reaction
  2. customTotal Synthesis of the Pseudopterane (−)-Kallolide B
  3. customSynthesis of talaromycins A, B, C, and E
  4. extractionextracted with water/Et2O (3×)
  5. washThe organic phases were washed with aqueous 10% NaCl
  6. dry with materialdried over Na2SO4
  7. customevaporated
  8. customPurification by flash-chromatography on silica gel (hexane/EtOAc 9:1 to 2:1)

Sources & evidence

ORD record
ord-44dbc41a5ec344b595a8c632e88f72ac
Source dataset
uspto-grants-2006_03
Patent number
US07012077B2

Reaction notes

Loading…