Sodium Hydroxide → 6-Hydroxy-2,5,7,8-tetramethylchroman-2-acetic acid

HRID 268406Notes

Reaction equation

HRID 268406 reaction equation
[H-].[Na+].COC(CP(OC)(OC)=O)=O.C(OC1C(C)=C2C(=C(C)C=1C)OC(O)(C)CC2)(=O)C.C([O:36][C:37]1[C:38]([CH3:55])=[C:39]2[C:44](=[C:45]([CH3:48])[C:46]=1[CH3:47])[O:43][C:42]([CH2:50][C:51]([O:53]C)=[O:52])([CH3:49])[CH2:41][CH2:40]2)(=O)C.[OH-].[Na+]>O1CCCC1.O.C(O)C>[OH:36][C:37]1[C:38]([CH3:55])=[C:39]2[C:44](=[C:45]([CH3:48])[C:46]=1[CH3:47])[O:43][C:42]([CH2:50][C:51]([OH:53])=[O:52])([CH3:49])[CH2:41][CH2:40]2

Participants

9

Reactant 5

HCID 14798Sodium HydroxideHCID 24758Sodium hydrideHCID 80029Trimethyl phosphonoacetateHCID 144156666-Acetoxy-2-hydroxy-2,5,7,8-tetramethylchromanHCID 14776652methyl 2-(6-acetoxy-2,5,7,8-tetramethyl-3,4-dihydro-2H-benzo[1,2-b]pyran-2-yl)acetate

Product 1

HCID 55926-Hydroxy-2,5,7,8-tetramethylchroman-2-acetic acid

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

In a dried flask under N2, a suspension of 47.2 (1.10 mol) of 56 percent by weight sodium hydride in mineral oil in 1000 ml of tetrahydrofuran was stirred as 209.4 g (1.15 mol) of trimethyl phosphonoacetate was added over 2.25 hr. The white paste was stirred for 0.25 hr and then a solution of 132.2 g (0.50 mol) of (±)-6-acetoxy-2-hydroxy-2,5,7,8-tetramethylchroman in 1000 ml of tetrahydrofuran was added over 0.50 hr. The pale yellow suspension was stirred at 23°C for 18 hours and then heated at reflux for 4.0 hours. The cooled solutions from two such reactions were stripped of solvent and worked up and dried by the procedure given in Example 1 to give a cloudy red-brown oil containing (±)-methyl (6-acetoxy-2,5,7,8-tetramethylchroman-2-yl)acetate. To a solution of this material in 2000 ml. of ethanol, there was added 2000 ml. of H2O and 240 g. (6.0 mol.) of NaOH. The solution was stirred at 23°C. for 4 hours, washed with petroleum ether (b.p. 30°-60°C.), diluted with 6000 ml. of ice-H2O and acidified by the dropwise addition over 0.50 hour of 600 ml. of concentrated aqueous HCl. The solid was removed by filtration, washed with H2O and crystallized from ethanol-H2O to give (±) -(6-hydroxy-2,5,7,8-tetramethylchroman-2-yl)acetic acid as a light tan powder: m.p. 168°-171°C.

Workup

  1. additionwas added over 2.25 hr
  2. stirringThe pale yellow suspension was stirred at 23°C for 18 hours
  3. temperatureheated
  4. temperatureat reflux for 4.0 hours
  5. customdried by the procedure
  6. customto give a cloudy red-brown oil
  7. stirringThe solution was stirred at 23°C. for 4 hours
  8. washwashed with petroleum ether (b.p. 30°-60°C.)
  9. additiondiluted with 6000 ml
  10. additionof ice-H2O and acidified by the dropwise addition over 0.50 hour of 600 ml
  11. customThe solid was removed by filtration
  12. washwashed with H2O
  13. customcrystallized from ethanol-H2O

Sources & evidence

ORD record
ord-ece11ff5d3984f83aeebb46976c86296
Source dataset
uspto-grants-1976_03
Patent number
US03947473

Reaction notes

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