Carbon Dioxide → Adapalene

HRID 1991924Notes

Reaction equation

HRID 1991924 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]CCCC.[C:37](=[O:39])=[O:38]>Cl.C1COCC1>[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 178418339Butyllithium

Product 1

HCID 60164Adapalene

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-40 °C

Procedure

A mixture of 6-[3-(1-adamantyl)-4-methoxyphenyl]-2-bromonaphthalene (50 mg, 0.11 mmol), 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 solution was cooled to −40° C. and n-BuLi (139.5 μl, 1.6 M in hexane, 0.22 mmol) was added, dropwise, during 30 minutes. 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 dried with Na2SO4 and next were evaporated to dryness, giving the crude of Adapalene. The crude was purified in the same way as that of the Example 8. 15 mg of Adapalene were obtained (30%) as a white solid.

Workup

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

Sources & evidence

ORD record
ord-da508942896d4b6f884e95fde43db153
Source dataset
uspto-grants-2010_01
Patent number
US07645910B2

Reaction notes

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