Aluminium lithium hydride → HCID 178483347, compound

HRID 896640Notes

Reaction equation

HRID 896640 reaction equation
CO[C:3](=O)[N:4]([C@H:14]1[CH2:19][CH2:18][C@H:17]([C:20]2[CH:25]=[CH:24][C:23]([OH:26])=[CH:22][CH:21]=2)[CH2:16][CH2:15]1)[CH2:5][CH2:6][CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.[H-].[H-].[H-].[H-].[Li+].[Al+3]>C1COCC1>[CH3:3][N:4]([CH2:5][CH2:6][CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C@H:14]1[CH2:19][CH2:18][C@H:17]([C:20]2[CH:21]=[CH:22][C:23]([OH:26])=[CH:24][CH:25]=2)[CH2:16][CH2:15]1

Participants

4

Reactant 2

HCID 21226445Aluminium lithium hydride2×HCID 178502088HCID 178502088, compound

Product 1

HCID 178483347HCID 178483347, compoundYield 71.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To an ice-cold, stirred solution of trans-N-[4-(4-hydroxyphenyl) cyclohexyl]-N-(3-phenylpropyl)carbamic acid methyl ester (0.30 g, 0.82 mmol) in anhydrous THF (20 mL), under a N2 atmosphere, was added LiAlH4 (95% powder, 0.034 g, 0.89 mmol). The reaction mixture was stirred at room temperature for 6 hours. LAH (95% powder, 0.07 mg, 1.8 mmol) was added, and stirring was continued for 14 hours. The reaction mixture was then quenched by the slow addition of H2O (2 mL). The mixture was partitioned between EtOAc and H2O, and the aqueous layer was extracted with EtOAc. The combined organic layers were dried (Na2SO4), filtered, and concentrated under reduced pressure. Purification by flash chromatography (silica, 9:1 MeOH:CH2Cl2) gave trans-4-{4-[methyl(3-phenylpropyl)amino]cyclohexyl}phenol (0.19 g, 70%) as an off-white solid: IR (thin film): 2931, 1613, 1515 cm−1; 5 1H NMR (300 MHz, CD3OD) δ 7.30-7.11 (m, 5H), 7.00 (d, J=8 Hz, 2H), 6.67 (d, J=8 Hz, 2H), 2.69-2.49 (m, 5H), 2.41-2.31 (m, 1H), 2.30 (s, 3H), 2.00-1.78 (m, 6H), 1.55-1.34 (m, 4H); CI-MS (methane) (m/z): 324 [M+H]+; HRMS-API (m/z): [M+H]+ Calcd for C22H29NO, 324.2327. found: 324.2333. HPLC: method A, 7.82 minutes (99.8%); method B, 13.89 minutes (99.7%); Anal. Calcd for C22H29NO.0.25 H2O: C, 80.57; H, 9.07; N, 4.27. Found: C, 80.51; H, 8.83; N, 4.27.

Workup

  1. stirringstirring
  2. waitwas continued for 14 hours
  3. customThe reaction mixture was then quenched by the slow addition of H2O (2 mL)
  4. customThe mixture was partitioned between EtOAc and H2O
  5. extractionthe aqueous layer was extracted with EtOAc
  6. dry with materialThe combined organic layers were dried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customPurification by flash chromatography (silica, 9:1 MeOH:CH2Cl2)

Sources & evidence

ORD record
ord-06926a7e78ce4f05b0f78626e51eabc6
Source dataset
uspto-grants-2005_07
Patent number
US06919377B2

Reaction notes

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