Toluene → HCID 66630331, compound

HRID 555384Notes

Reaction equation

HRID 555384 reaction equation
C([O:3][C:4]([CH:6]1[CH2:11][CH2:10][CH:9]([O:12][C:13]2[CH:18]=[CH:17][C:16]([C:19](=[O:31])[NH:20][CH:21]3[CH:28]4[CH2:29][CH:24]5[CH2:25][CH:26]([CH2:30][CH:22]3[CH2:23]5)[CH2:27]4)=[CH:15][CH:14]=2)[CH2:8][CH2:7]1)=O)C.CC(C[AlH]CC(C)C)C.C1(C)C=CC=CC=1.[NH4+].[Cl-]>C1COCC1>[CH:22]12[CH2:30][CH:26]3[CH2:25][CH:24]([CH2:29][CH:28]([CH2:27]3)[CH:21]1[NH:20][C:19](=[O:31])[C:16]1[CH:17]=[CH:18][C:13]([O:12][CH:9]3[CH2:8][CH2:7][CH:6]([CH2:4][OH:3])[CH2:11][CH2:10]3)=[CH:14][CH:15]=1)[CH2:23]2

Participants

6

Reactant 4

HCID 1140TolueneHCID 14487Diisobutylaluminum hydride2×HCID 25517Ammonium ChlorideHCID 66629762HCID 66629762, compound

Product 1

HCID 66630331HCID 66630331, compoundYield 60%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-35 °C

Procedure

In a flame dried flask was 4-[4-(adamantan-2-ylcarbamoyl)-phenoxy]-cyclohexane carboxylic acid ethyl ester (2 g, 4.7 mmol) dissolved in dry THF (300 mL) and cooled to −35° C. To this solution was added 1M DIBAL in toluene (14 mL, 14.1 mmol) and the mixture was stirred at −35° C. for 3 hrs. and left in a freezer at −18° C. for 16 hrs. Due to incomplete reaction an additional portion of 1M DIBAL (5 mL) was added and the mixture was stirred at −18° C. for 1 hr. The reaction was quinched by slowly addition of sat. aq. NH4Cl followed by evaporation to ¼ of the volume and extracted with DCM (3×50 mL). The combined organic phases were evaporated in vacuo and the residue purified using column chromatography (Isco, 120 gram column) and a solvent gradient of heptane/AcOEt from 0 to 100%. Desired fractions were collected and the solvent evaporated in vacuo affording 1 g (60%) of N-adamantan-2-yl-4-(4-hydroxymethyl-cyclohexyloxy)-benzamide as an oil.

Workup

  1. customIn a flame dried flask
  2. waitand left in a freezer at −18° C. for 16 hrs
  3. additionwas added
  4. stirringthe mixture was stirred at −18° C. for 1 hr
  5. customfollowed by evaporation
  6. extractionextracted with DCM (3×50 mL)
  7. customThe combined organic phases were evaporated in vacuo
  8. customthe residue purified
  9. customDesired fractions were collected
  10. customthe solvent evaporated in vacuo

Sources & evidence

ORD record
ord-bb114dab6a0349319b1cb5810e90dd61
Source dataset
uspto-grants-2011_11
Patent number
US08053447B2

Reaction notes

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