Triethylamine → HCID 178518610, compound

HRID 1007533Notes

Reaction equation

HRID 1007533 reaction equation
Cl.[Cl:2][C:3]1[CH:8]=[CH:7][C:6]([CH2:9][CH2:10][CH2:11][NH2:12])=[CH:5][CH:4]=1.CCN(CC)CC.[CH:20]1([C:27]2[CH:36]=[CH:35][C:30]3[NH:31][C:32](=[O:34])[O:33][C:29]=3[CH:28]=2)[CH2:25][CH2:24][C:23](=O)[CH2:22][CH2:21]1.[BH4-].[Na+]>CC(O)C.C1COCC1>[Cl:2][C:3]1[CH:4]=[CH:5][C:6]([CH2:9][CH2:10][CH2:11][NH:12][C@H:23]2[CH2:24][CH2:25][C@H:20]([C:27]3[CH:36]=[CH:35][C:30]4[NH:31][C:32](=[O:34])[O:33][C:29]=4[CH:28]=3)[CH2:21][CH2:22]2)=[CH:7][CH:8]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 4311764Sodium borohydrideHCID 98133826-(4-oxocyclohexyl)-1,3-benzoxazol-2(3H)-one2×HCID 222488113-(4-Chlorophenyl)propylamine hydrochloride

Product 1

HCID 178518610HCID 178518610, compoundYield 24.3%

Reagents, catalysts & solvents 2

HCID 3776IsopropanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 3-(4-Chlorophenyl)-1-propylamine hydrochloride (1.5 g, 7.3 mmol) in 2-propanol (50 mL) was added Et3N (1.1 mL, 8.0 mmol), ketone 5 (1.7 g, 7.3 mmol), THF (25 mL), and 3 Å molecular sieves. The reaction mixture was warmed to dissolve ketone 5 and then stirred at room temperature for 2.25 hours. Sodium borohydride (550 mg, 14.5 mmol) was added, and the reaction mixture was stirred for 12 hours. The reaction was quenched with MeOH, and the mixture was filtered through a pad of Celite and concentrated under reduced pressure. Purification by flash chromatography (silica, 90:10 CH2Cl2/MeOH) followed by trituration/recrystallization with MeOH gave 6-{trans-4-[3-(4-chlorophenyl)propylamino]cyclohexyl}-3H-benzoxazol-2-one (683 mg, 24%), as a white solid: 1H NMR (500 MHz, DMSO-d6): δ 7.32 (d, J=8 Hz, 2H), 7.23 (d, J=8 Hz, 2H), 7.12 (s, 1H), 6.98-6.93 (m, 2H), 2.61 (t, J=7 Hz, 2H), 2.56 (t, J=7 Hz, 2H), 2.48-2.38 (m, 2H), 1.94 (br d, J=10 Hz, 2H), 1.77 (br d, J=10 Hz, 2H), 1.72-1.66 (m, 2H), 1.44 (dddd, J=12, 12, 12, 3 Hz, 2H), 1.12 (dddd, J=12, 12, 12, 3 Hz, 2H).

Workup

  1. temperatureThe reaction mixture was warmed
  2. stirringthe reaction mixture was stirred for 12 hours
  3. customThe reaction was quenched with MeOH
  4. filtrationthe mixture was filtered through a pad of Celite
  5. concentrationconcentrated under reduced pressure
  6. customPurification by flash chromatography (silica, 90:10 CH2Cl2/MeOH)
  7. customfollowed by trituration/recrystallization with MeOH

Sources & evidence

ORD record
ord-e502cceab0b74c68acf73ad80b8350c3
Source dataset
uspto-grants-2004_09
Patent number
US06794402B2

Reaction notes

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