Diisobutylaluminum hydride → HCID 178516013, compound

HRID 1884515Notes

Reaction equation

HRID 1884515 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][C:10]([NH:12][C@H:13]2[CH2:18][CH2:17][C@H:16]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[CH2:15][CH2:14]2)=O)=[CH:4][CH:3]=1.CC(C[AlH]CC(C)C)C>C1(C)C=CC=CC=1>[NH4+:12].[OH-:1].[C:19]1([C@H:16]2[CH2:15][CH2:14][C@H:13]([NH:12][CH2:10][CH2:9][CH2:8][C:5]3[CH:4]=[CH:3][C:2]([OH:1])=[CH:7][CH:6]=3)[CH2:18][CH2:17]2)[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1

Participants

5

Reactant 2

HCID 14487Diisobutylaluminum hydride2×HCID 178520485HCID 178520485, compound

Product 2

HCID 14923Ammonium HydroxideHCID 178516013HCID 178516013, compoundYield 35.5%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent3×

Procedure

To a suspension of trans-3-(4-hydroxyphenyl)-N-(4-phenylcyclohexyl)propionamide (0.65 g, 2.0 mmol) in toluene (5 mL), under a nitrogen atmosphere, was added DIBAL-H (12.0 mL of a 1 M in toluene, 12 mmol) with stirring. The reaction mixture was heated under reflux overnight. Additional DIBAL-H (12 mL of a 1.0 M solution in toluene, 12 mmol) was added, and heating was continued for a further 1.5 hours. The reaction mixture was cooled to room temperature and quenched by the slow addition of MeOH (50 mL). The mixture was heated at reflux for 15 minutes, cooled to room temperature, filtered, and concentrated under reduced pressure. Purification by flash chromatography (silica, 10% MeOH:CH2Cl2) then (silica, 89:10:1 CH2Cl2: MeOH:NH4OH) gave (b) trans 4-[3-(4-phenylcyclohexylamino)propyl]phenol (110 mg) as a tan solid: mp 211-214° C.; IR (KBr): 2926, 1516, cm−1; 1H NMR (300 MHz, CD3OD) δ 7.23-7.10 (m, 5H), 7.02 (d, J=8 Hz, 2H), 6.69 (d, J=8 Hz, 2H), 2.68-2.44 (m, 6H), 2.04 (br d, J=13 Hz, 2H), 1.88 (br d, J=13 Hz, 2H), 1.82-1.73 (m, 2H), 1.57 (dddd, J=13, 13, 13, 3 Hz, 2H), 1.26 (dddd, J=13, 13, 13, 3 Hz, 2H); CI—MS (methane) (m/z): 310 [M+H]+; HRMS-API (m/z): [M+H]+ calculated for C21H27NO, 310.2171; found, 310.2166; HPLC: method A, 7.93 minutes (95.2%); method B, 14.29 minutes (97.3%); Anal. Calcd. for C21H27NO.0.80H2O: C, 77.88; H, 8.90; N, 4.32. Found: C, 77.52; H, 8.66; N, 4.12.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureunder reflux overnight
  3. temperatureheating
  4. customquenched by the slow addition of MeOH (50 mL)
  5. temperatureThe mixture was heated
  6. temperatureat reflux for 15 minutes
  7. temperaturecooled to room temperature
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customPurification by flash chromatography (silica, 10% MeOH:CH2Cl2)

Sources & evidence

ORD record
ord-17ebdae6f1b2435db87106bcc1026489
Source dataset
uspto-grants-2004_07
Patent number
US06765022B2

Reaction notes

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