Sodium Hydroxide → HCID 178483355, compound

HRID 1007534Notes

Reaction equation

HRID 1007534 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][CH2:10][NH:11][C@H:12]2[CH2:17][CH2:16][C@H:15]([C:18]3[CH:27]=[CH:26][C:21]4[NH:22][C:23](=[O:25])[O:24][C:20]=4[CH:19]=3)[CH2:14][CH2:13]2)=[CH:4][CH:3]=1.[BH-](OC(C)=O)(OC(C)=O)O[C:30](C)=O.[Na+].[OH-].[Na+]>CO.C(Cl)Cl.O>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][CH2:10][N:11]([CH3:30])[C@H:12]2[CH2:17][CH2:16][C@H:15]([C:18]3[CH:27]=[CH:26][C:21]4[NH:22][C:23](=[O:25])[O:24][C:20]=4[CH:19]=3)[CH2:14][CH2:13]2)=[CH:4][CH:3]=1

Participants

7

Reactant 3

HCID 14798Sodium HydroxideHCID 5049666Sodium triacetoxyborohydrideHCID 178518610HCID 178518610, compound

Product 1

HCID 178483355HCID 178483355, compoundYield 66%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of 6-{trans-4-[3-(4-chlorophenyl)-propylamino]-cyclohexyl}-3H-benzoxazol-2-one (655 mg, 1.7 mmol) in MeOH (20 mL) and CH2Cl2 (25 mL) was added p-formaldehyde (0.70 mL of a 37 wt % solution in H2O, 8.5 mmol). The reaction mixture was warmed to dissolve compound the amine, and then stirred at room temperature for 15 minutes. NaBH(OAc)3 was added and stirring was continued for 12 hours. The reaction mixture was brought to pH 8 with solid NaOH, concentrated under reduced pressure, and purified by flash chromatography (silica, 95:4.5:0.5 CH2Cl2:MeOH:NH4OH). Formation of the HCl salt, followed by recrystallization (MeOH:Et2O) gave 6-(trans-4-{[3-(4-chlorophenyl)propyl]-methylamino}-cyclohexyl)-3H-benzoxazol-2-one (461 mg, 66%), as a white solid: mp 267-271° C.; IR (KBr): 2949, 1769, 1494, 1452 cm−1; 1H NMR (500 MHz, DMSO-d6): δ 11.50 (s, 1H), 10.39 (s, 1H), 7.37 (d, J=8 Hz, 2H), 7.30 (d, J=8 Hz, 2H), 7.16 (s, 1H), 7.00 (br s, 2H), 3.33-3.26 (m, 1H), 3.18-3.10 (m, 1H), 3.04-2.95 (m, 1H), 2.69 (d, J=5 Hz, 3H), 2.68-2.62 (m, 2H), 2.58-2.51 (m, 1H), 2.18-1.98 (m, 4H), 1.93-1.87 (m, 2H), 1.69-1.51 (m, 4H); HRMS-APCI (m/z): [M+H]+ calcd for C23H27ClN2O2, 399.1839; found, 399.1831; HPLC: method A, 6.35 minutes (98.6%); method B. 11.82 minutes (99.1%); Anal. Calcd for C23H27ClN2O2.HCl.0.25H2O: C, 62.80; H, 6.53; N, 6.37. Found: C, 62.94; H, 6.57; N, 6.21.

Workup

  1. temperatureThe reaction mixture was warmed
  2. stirringstirring
  3. waitwas continued for 12 hours
  4. concentrationconcentrated under reduced pressure
  5. custompurified by flash chromatography (silica, 95:4.5:0.5 CH2Cl2:MeOH:NH4OH)
  6. customFormation of the HCl salt, followed by recrystallization (MeOH:Et2O)

Sources & evidence

ORD record
ord-317fe4b0295a4259bf83d79ec0c493d9
Source dataset
uspto-grants-2004_09
Patent number
US06794402B2

Reaction notes

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