3-Furaldehyde → HCID 178518614, compound

HRID 1007527Notes

Reaction equation

HRID 1007527 reaction equation
[F: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.C([O-])([O-])=O.[K+].[K+].Cl.FC1C=CC(CCCN[C@H]2CC[C@H:49]([C:52]3[CH:61]=CC4NC(=O)[O:58][C:54]=4[CH:53]=3)CC2)=CC=1.O1C=CC(C=O)=C1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].[OH-].[Na+]>C1COCC1.CO>[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][CH2:10][N:11]([CH2:49][C:52]2[CH:53]=[CH:54][O:58][CH:61]=2)[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

9

Reactant 6

HCID 103513-FuraldehydeHCID 11430Potassium CarbonateHCID 14798Sodium HydroxideHCID 5049666Sodium triacetoxyborohydride2×HCID 178479656HCID 178479656, compoundHCID 178518612HCID 178518612, compound

Product 1

HCID 178518614HCID 178518614, compoundYield 46%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

The free base of 6-{trans-4-[3-(4-fluorophenyl)propylamino]cyclohexyl}-3H-benzoxazol-2-one was made by the addition of K2CO3 (170 mg, 1.2 mmol) to 6-{trans-4-[3-(4-fluorophenyl)propylamino]cyclohexyl}-3H-benzoxazol-2-one hydrochloride (500 mg, 1.2 mmol) in THF (50 mL). To this suspension was added 3-furaldehyde (470 mg, 4.9 mmol) and, after 10 minutes, NaBH(OAc)3 (520 mg, 2.4 mmol) was added. After stirring the reaction mixture 3 hours, additional NaBH(OAc)3 (520 mg, 2.4 mmol) was added, and stirring continued for 14.5 hours. The solution was diluted with MeOH and brought to pH=13 with solid NaOH. The solution was then concentrated under reduced pressure. Purification by flash chromatography (silica, 90:9.5:0.5 CH2Cl2:MeOH:NH4OH), followed by formation of the HCl salt, gave 6-(trans-4-{[3-(4-fluorophenyl)-propyl]furan-3-ylmethylamino}cyclohexyl)-3H-benzoxazol-2-one (272 mg, 46%) as an off-white solid: mp 225-227° C.; IR (KBr): 2929, 1773, 1510 cm−1; 1H NMR (500 MHz, DMSO-d6): δ 11.49 (s, 1H), 9.99 (br s, 1H), 7.90 (s, 1H), 7.76 (s, 1H), 7.27-7.24 (m, 2H), 7.18 (s, 1H), 7.14-7.10 (m, 2H), 7.02-6.98 (m, 2H), 6.75 (s, 1H), 4.30-4.18 (m, 2H), 3.33-3.29 (m, 1H), 3.20-3.12 (m, 1H), 3.01-2.93 (m, 1H), 2.67-2.53 (m, 3H), 2.22-2.15 (m, 2H), 2.07-1.88 (m, 4H), 1.78-1.66 (m, 2H), 1.62-1.49 (m, 2H); ESI-MS (m/z): 449 [M+H]+; HPLC: method A, 6.27 minutes (99.8%); Anal. Calcd for C27H29FN2O3.HCl: C, 66.87; H, 6.23; N, 5.78. Found: C, 66.54; H, 6.27; N, 5.48.

Workup

  1. additionwas added
  2. waitcontinued for 14.5 hours
  3. concentrationThe solution was then concentrated under reduced pressure
  4. customPurification by flash chromatography (silica, 90:9.5:0.5 CH2Cl2:MeOH:NH4OH)

Sources & evidence

ORD record
ord-a3e5661d31d543f3bc9a69aa4ec71de0
Source dataset
uspto-grants-2004_09
Patent number
US06794402B2

Reaction notes

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