Sodium Hydroxide → HCID 178439071, compound

HRID 1007549Notes

Reaction equation

HRID 1007549 reaction equation
[CH3:1][NH:2][C@H:3]1[CH2:8][CH2:7][C@H:6]([C:9]2[CH:18]=[CH:17][C:12]3[NH:13][C:14](=[O:16])[O:15][C:11]=3[CH:10]=2)[CH2:5][CH2:4]1.C([O-])(O)=O.[Na+].[CH:24]([C:27]1[CH:32]=[CH:31][C:30]([CH2:33][CH2:34][CH:35]=O)=[CH:29][CH:28]=1)([CH3:26])[CH3:25].[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].[OH-].[Na+]>CO.C(Cl)Cl>[CH:24]([C:27]1[CH:28]=[CH:29][C:30]([CH2:33][CH2:34][CH2:35][N:2]([CH3:1])[C@H:3]2[CH2:4][CH2:5][C@H:6]([C:9]3[CH:18]=[CH:17][C:12]4[NH:13][C:14](=[O:16])[O:15][C:11]=4[CH:10]=3)[CH2:7][CH2:8]2)=[CH:31][CH:32]=1)([CH3:25])[CH3:26]

Participants

8

Reactant 5

HCID 14798Sodium HydroxideHCID 62654Benzenepropanal, 4-(1-methylethyl)-HCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 178484782HCID 178484782, compound

Product 1

HCID 178439071HCID 178439071, compoundYield 52.7%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of amine 15 (670 mg, 2.40 mmol) in 1:1 CH2Cl2:MeOH (30 mL) was added solid NaHCO3 (200 mg, 2.40 mmol) and, after 10 minutes, 3-(4-isopropylphenyl)propionaldehyde (420 mg, 2.40 mmol). After stirring for 5 minutes, NaBH(OAc)3 (760 mg, 3.60 mmol) was added, and the mixture was stirred at room temperature for 12 hours. The reaction mixture was brought to pH 8 with solid NaOH and concentrated under reduced pressure. Purification by flash chromatography (silica, 95:5 CH2Cl2:MeOH followed by 89:10:1 CH2Cl2:MeOH:NH4OH), followed by formation of the HCl salt and recrystallization (MeOH:Et2O) gave 6-(trans-4-{[3-(4-isopropylphenyl)-propyl]methylamino}cyclohexyl)-3H-benzoxazol-2-one (514 mg, 48%), as a white solid: mp 179-181° C.; IR (KBr): 2959, 1771, 1498, 1451 cm−1; 1H NMR (500 MHz, DMSO-d6): δ 11.48 (s, 1H), 10.10 (s, 1H), 7.17-7.15 (m, 5H), 7.00 (br s, 2H), 3.32-3.29 (m, 1H), 3.19-3.11 (m, 1H), 3.06-2.99 (m, 1H), 2.89-2.83 (m, 1H), 2.70 (d, J=4 Hz, 3H), 2.63-2.52 (m, 3H), 2.15-1.95 (m, 4H), 1.93-1.87 (m, 2H), 1.66-1.50 (m, 4H), 1.19 (d, J=7 Hz, 6H); ESI (m/z): 407 [M+H]+; method B, 12.69 minutes (>99%); Anal. Calcd for C26H34N2O2.HCl: C, 70.49; H, 7.96; N, 6.32. Found: C, 70.29; H, 8.05; N, 6.28.

Workup

  1. stirringthe mixture was stirred at room temperature for 12 hours
  2. concentrationconcentrated under reduced pressure
  3. customPurification by flash chromatography (silica, 95:5 CH2Cl2:MeOH followed by 89:10:1 CH2Cl2:MeOH:NH4OH)
  4. customfollowed by formation of the HCl salt and recrystallization (MeOH:Et2O)

Sources & evidence

ORD record
ord-e4a2a38654b94779ad6326e35edf74d5
Source dataset
uspto-grants-2004_09
Patent number
US06794402B2

Reaction notes

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