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

HRID 328841Notes

Reaction equation

HRID 328841 reaction equation
[H-].[Na+].C[O:4][C:5]([CH2:7]P(OC)(OC)=O)=[O:6].C([O:17][C:18]1[C:19]([CH3:32])=[C:20]2[C:25](=[C:26]([CH3:29])[C:27]=1[CH3:28])[O:24][C:23](O)([CH3:30])[CH2:22][CH2:21]2)(=O)C.C(OC1(C)C(C)CC2C(=C(C)C(C)=C(OC(=O)C)C=2C)O1)(=O)C.[OH-].[Na+]>O1CCCC1.C(O)C>[OH:17][C:18]1[C:19]([CH3:32])=[C:20]2[C:25](=[C:26]([CH3:29])[C:27]=1[CH3:28])[O:24][C:23]([CH2:7][C:5]([OH:4])=[O:6])([CH3:30])[CH2:22][CH2:21]2

Participants

8

Reactant 5

HCID 14798Sodium HydroxideHCID 24758Sodium hydrideHCID 80029Trimethyl phosphonoacetateHCID 144156666-Acetoxy-2-hydroxy-2,5,7,8-tetramethylchromanHCID 54353318(+/-)-Methyl-(6-acetoxy-2, 5,7,8-tetramethylchroman-2-yl) acetate

Product 1

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

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

In a dried flask under N 2, a suspension of 47.2 g (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-tetra- methylchroman 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 H 2 0 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-H 2 O 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 H 2 O and crystallized from ethanol-H 2 O 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-H 2 O and acidified by the dropwise addition over 0.50 hour of 600 ml
  11. customThe solid was removed by filtration
  12. washwashed with H 2 O
  13. customcrystallized from ethanol-H 2 O

Sources & evidence

ORD record
ord-b6eede0c48d440f494e6ee945bb2a3c8
Source dataset
uspto-grants-1977_04
Patent number
US04018799

Reaction notes

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