Water → HCID 9858482, compound

HRID 896646Notes

Reaction equation

HRID 896646 reaction equation
[O:1]([CH2:8][CH2:9][NH:10][CH:11]1[CH2:16][CH2:15][CH:14]([C:17]2[CH:22]=[CH:21][C:20]([OH:23])=[CH:19][CH:18]=2)[CH2:13][CH2:12]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.O.[C:25](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[OH-].[Na+]>CO.C(Cl)Cl>[CH3:25][N:10]([CH2:9][CH2:8][O:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)[CH:11]1[CH2:16][CH2:15][CH:14]([C:17]2[CH:22]=[CH:21][C:20]([OH:23])=[CH:19][CH:18]=2)[CH2:13][CH2:12]1

Participants

7

Reactant 4

HCID 962WaterHCID 14798Sodium HydroxideHCID 5049666Sodium triacetoxyborohydrideHCID 9879760HCID 9879760, compound

Product 1

HCID 9858482HCID 9858482, compoundYield 72%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of 4-[4-(2-phenoxyethylamino)cyclohexyl]phenol (0.35 g, 1.13 mmol) in a mixture of MeOH (10 mL), water (1 mL) and CH2Cl2 (5 mL) was added p-formaldehyde (0.17 g, 5.62 mmol). The reaction mixture was stirred for 2 hours, sodium triacetoxyborohydride (0.33 g, 1.58 mmol) was added and stirring was continued overnight. Solid NaOH was added, until the solution turned clear. Silica gel was added, and the solvents were removed under reduced pressure. Purification by flash chromatography (10:1 CH3Cl:MeOH) gave 4-{4-[methyl(2-phenoxyethyl)amino]cyclohexyl}-phenol (264 mg, 72%) as a white solid: mp 216-220° C.; IR (KBr): 3149, 2936, 1599 cm−1; 1H NMR (500 MHz, DMSO-d6) δ 9.14 (br s, 1H), 7.34 (dd, J=9, 9 Hz, 2H), 7.00 (d, J=9 Hz, 5H), 6.68 (d, J=9 Hz, 2H), 4.42 (br s, 2H), 3.61-3.33 (m, 3H), 2.82 (s, 3H), 2.92 (t, J=5 Hz, 2H), 2.49 (tt, J10, 2 Hz, 1H), 2.19 (dd, J=10, 2 Hz), 1.88 (br d, J=10 Hz, 2H), 1.74 (dddd, J=10, 10, 10, 2 Hz, 2H), 1.47 (dddd, J=10, 10, 10, 2 Hz, 2H); CI-MS (methane) (m/z): 326 [M+H]+; HPLC: method A, 5.64 min (95.3%); method B, 9.63 min (99.2%); Anal. Calcd for C24H33NO.HCl: C, 69.69; H, 7.80; N, 3.87. Found: C, 69.44; H, 7.81; N, 3.80.

Workup

  1. stirringstirring
  2. waitwas continued overnight
  3. additionSilica gel was added
  4. customthe solvents were removed under reduced pressure
  5. customPurification by flash chromatography (10:1 CH3Cl:MeOH)

Sources & evidence

ORD record
ord-a0ead065279648ceb87ea26276031716
Source dataset
uspto-grants-2005_07
Patent number
US06919377B2

Reaction notes

Loading…