4-Methoxybenzyl alcohol → HCID 86732774, compound

HRID 525909Notes

Reaction equation

HRID 525909 reaction equation
FC(F)(F)C([O:5][C@@H:6]1[CH2:10][C:9](=[O:11])[O:8][C:7]1=[O:12])=O.[CH3:15][O:16][C:17]1[CH:22]=[CH:21][C:20]([CH2:23][OH:24])=[CH:19][CH:18]=1.C(N/C(=N\C(C)C)/O[C:31]([CH3:34])([CH3:33])[CH3:32])(C)C>ClCCl>[OH:5][C@H:6]([CH2:10][C:9]([O:8][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:11])[C:7]([O:24][CH2:23][C:20]1[CH:21]=[CH:22][C:17]([O:16][CH3:15])=[CH:18][CH:19]=1)=[O:12]

Participants

5

Reactant 3

HCID 77384-Methoxybenzyl alcoholHCID 86732773HCID 86732773, compoundHCID 178457539HCID 178457539, compound

Product 1

HCID 86732774HCID 86732774, compoundYield 50.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (R)-2,5-dioxotetrahydrofuran-3-yl 2,2,2-trifluoroacetate (85 g, 401 mmol) in Dichloromethane (DCM) (600 mL) was added (4-methoxyphenyl)methanol (150 mL, 1202 mmol). The mixture was stirred at rt for 3 h and then extracted three times with 10% aqueous solution of NaHCO3. The combined aqueous extracts were washed with DCM, acidified to pH 2 with 2 N HCl, and then extracted with DCM. The organic layer was dried over sodium sulfate and filtered. To the filtrate was added (E)-tert-butyl N,N′-diisopropylcarbamimidate (161 g, 802 mmol) dropwise over 1 h. The mixture was stirred at rt overnight. The precipitate was removed by filtration and the filtrate was purified by normal phase automatic silica column chromatography (Combiflash RF), eluting with EA/Hexane (10-80%) to afford (R)-4-tert-butyl 1-(4-methoxybenzyl) 2-hydroxysuccinate (62.5 g, 201 mmol, 50.2% yield) as a colorless oil. LCMS: (M+Na)+: 333.1

Workup

  1. extractionextracted three times with 10% aqueous solution of NaHCO3
  2. washThe combined aqueous extracts were washed with DCM
  3. extractionextracted with DCM
  4. dry with materialThe organic layer was dried over sodium sulfate
  5. filtrationfiltered
  6. stirringThe mixture was stirred at rt overnight
  7. customThe precipitate was removed by filtration
  8. customthe filtrate was purified by normal phase automatic silica column chromatography (Combiflash RF)
  9. washeluting with EA/Hexane (10-80%)

Sources & evidence

ORD record
ord-394f14eee1fe4befa3aa2bca8ebbfd59
Source dataset
uspto-grants-2016_05
Patent number
US09340556B2

Reaction notes

Loading…