Carbon Dioxide → Adapalene

HRID 1991923Notes

Reaction equation

HRID 1991923 reaction equation
[C:1]12([C:11]3[CH:12]=[C:13]([C:19]4[CH:20]=[C:21]5[C:26](=[CH:27][CH:28]=4)[CH:25]=[C:24](Br)[CH:23]=[CH:22]5)[CH:14]=[CH:15][C:16]=3[O:17][CH3:18])[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[CH2:2]1)[CH2:8]2.[H-].[Na+].[Li]C(C)(C)C.[C:37](=[O:39])=[O:38]>C1COCC1.Cl>[CH3:18][O:17][C:16]1[CH:15]=[CH:14][C:13]([C:19]2[CH:28]=[CH:27][C:26]3[CH:25]=[C:24]([C:37]([OH:39])=[O:38])[CH:23]=[CH:22][C:21]=3[CH:20]=2)=[CH:12][C:11]=1[C:1]12[CH2:2][CH:3]3[CH2:9][CH:7]([CH2:6][CH:5]([CH2:4]3)[CH2:10]1)[CH2:8]2

Participants

7

Reactant 4

HCID 280Carbon Dioxide2×HCID 24758Sodium hydrideHCID 591298026-[3-(1-Adamantyl)-4-methoxyphenyl]-2-bromonaphthaleneHCID 178418306HCID 178418306, compound

Product 1

HCID 60164Adapalene

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-60 °C

Procedure

A mixture of 6-[3-(1-adamantyl)-4-methoxyphenyl]-2-bromonaphthalene (50 mg, 0.11 mmol) in THF (1 ml) was introduced into a Schlenk tube and was heated until its complete dissolution. Next, NaH (4.5 mg, 60% dispersion in mineral oil, 0.11 mmol) was added under argon atmosphere and at room temperature, and the mixture was stirred for 10 minutes. The obtained mixture was cooled to −60° C. and t-BuLi (1.7 M in penthane, 0.22 mmol) was added, dropwise, during a period of 30 minutes. Next, and at the same temperature, a continuous mild flow of CO2 (anhydrous gas) was introduced in the reaction for 1 h. After bringing the reaction to room temperature during 30 minutes with continuous flow of CO2, the mixture was diluted with aq HCl (5 ml, 2 M) and was vigorously stirred for 10 minutes. The resulting mixture was extracted with CHCl3 (3×5 ml) and the joined organic phases were evaporated to dryness once dried with Na2SO4, giving the crude of Adapalene.

Workup

  1. additionwas introduced into a Schlenk tube
  2. temperaturewas heated until its complete dissolution
  3. waitdropwise, during a period of 30 minutes
  4. stirringwas vigorously stirred for 10 minutes
  5. extractionThe resulting mixture was extracted with CHCl3 (3×5 ml)
  6. customthe joined organic phases were evaporated to dryness
  7. dry with materialonce dried with Na2SO4

Sources & evidence

ORD record
ord-82640073440548fb9ce8d7384318251c
Source dataset
uspto-grants-2010_01
Patent number
US07645910B2

Reaction notes

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