Ammonium Chloride → 9-{3-[6-(Hydroxymethyl)pyridin-2-yl]-2-methoxyphenyl}-3,3,6,6-tetramethyl-3,4,5,6,7,9-hexahydro-1H-xanthene-1,8(2H)-dione

HRID 873539Notes

Reaction equation

HRID 873539 reaction equation
[C:1](N1C=CN=C1)(N1C=CN=C1)=[O:2].CO[C:15]1[CH:20]=[CH:19][C:18]([C:21]2[N:26]=[C:25]([C:27](O)=[O:28])[CH:24]=[CH:23][CH:22]=2)=[CH:17][C:16]=1[CH:30]1[C:43]2[C:42](=[O:44])[CH2:41][C:40]([CH3:46])([CH3:45])[CH2:39][C:38]=2[O:37][C:36]2[CH2:35][C:34]([CH3:48])([CH3:47])[CH2:33][C:32](=[O:49])[C:31]1=2.[BH4-].[Na+].[Cl-].[NH4+]>C1COCC1.O>[OH:28][CH2:27][C:25]1[N:26]=[C:21]([C:18]2[C:17]([O:2][CH3:1])=[C:16]([CH:30]3[C:43]4[C:42](=[O:44])[CH2:41][C:40]([CH3:46])([CH3:45])[CH2:39][C:38]=4[O:37][C:36]4[CH2:35][C:34]([CH3:47])([CH3:48])[CH2:33][C:32](=[O:49])[C:31]3=4)[CH:15]=[CH:20][CH:19]=2)[CH:22]=[CH:23][CH:24]=1

Participants

7

Reactant 4

HCID 25517Ammonium ChlorideHCID 682631,1'-CarbonyldiimidazoleHCID 4311764Sodium borohydrideHCID 117700629HCID 117700629, compound

Product 1

HCID 1177006469-{3-[6-(Hydroxymethyl)pyridin-2-yl]-2-methoxyphenyl}-3,3,6,6-tetramethyl-3,4,5,6,7,9-hexahydro-1H-xanthene-1,8(2H)-dioneYield 78.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

1,1′-Carbonyldiimidazole (38.8 mg, 0.239 mol) was added to a solution of the 6-[4-methoxy-3-(3,3,6,6-tetramethyl-1,8-dioxo-2,3,4,5,6,7,8,9-octahydro-1H-xanthen-9-yl)phenyl]pyridine-2-carboxylic acid obtained in Example 1-2 (100 mg, 0.199 mmol) in THF (1.0 mL) at room temperature, and the mixture thus obtained was then stirred at the same temperature as above for 30 minutes. Subsequently, the reaction solution was cooled to 0° C., sodium borohydride (7.5 mg, 0.199 mmol) and water (0.1 mL) were then added thereto, and the mixture thus obtained was then stirred at the same temperature as above for 30 minutes. Thereafter, a saturated aqueous solution of ammonium chloride was added to the reaction solution, and the mixed solution was then extracted with ethyl acetate twice. The organic layer thus obtained was washed with brine, and was then dried over anhydrous sodium sulfate. The solvent was distilled away under reduced pressure. The residue thus obtained was purified by silica gel column chromatography (hexane:ethyl acetate=3:1 to 3:7, v/v), and was then solidified with a mixed solution of diethyl ether-hexane to obtain the title compound (76.3 mg, yield: 78%).

Workup

  1. customthe mixture thus obtained
  2. customthe mixture thus obtained
  3. stirringwas then stirred at the same temperature as above for 30 minutes
  4. extractionthe mixed solution was then extracted with ethyl acetate twice
  5. customThe organic layer thus obtained
  6. washwas washed with brine
  7. dry with materialwas then dried over anhydrous sodium sulfate
  8. distillationThe solvent was distilled away under reduced pressure
  9. customThe residue thus obtained
  10. customwas purified by silica gel column chromatography (hexane:ethyl acetate=3:1 to 3:7, v/v)

Sources & evidence

ORD record
ord-5cb78c342b3f4728a8a6bf50350ffb65
Source dataset
uspto-grants-2015_03
Patent number
US08975263B2

Reaction notes

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