Acetic Acid → 5-(3,4-Dichlorophenyl)-1-(cyclohexylmethyl)-5-[2-(3-morpholinoazetidin-1-yl]ethyl)-3-oxapiperidin-2-one

HRID 1457085Notes

Reaction equation

HRID 1457085 reaction equation
C(N(CC)CC)C.[Cl:8][C:9]1[CH:10]=[C:11]([C:16]2([CH2:30][CH:31]=O)[CH2:21][N:20]([CH2:22][CH:23]3[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]3)[C:19](=[O:29])[O:18][CH2:17]2)[CH:12]=[CH:13][C:14]=1[Cl:15].Cl.Cl.[O:35]1[CH2:40][CH2:39][N:38]([CH:41]2[CH2:44][NH:43][CH2:42]2)[CH2:37][CH2:36]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(O)(=O)C.C(=O)(O)[O-].[Na+]>O1CCCC1>[Cl:8][C:9]1[CH:10]=[C:11]([C:16]2([CH2:30][CH2:31][N:43]3[CH2:44][CH:41]([N:38]4[CH2:39][CH2:40][O:35][CH2:36][CH2:37]4)[CH2:42]3)[CH2:21][N:20]([CH2:22][CH:23]3[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]3)[C:19](=[O:29])[O:18][CH2:17]2)[CH:12]=[CH:13][C:14]=1[Cl:15]

Participants

8

Reactant 6

HCID 176Acetic AcidHCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 220613264-(Azetidin-3-yl)morpholine dihydrochlorideHCID 571935325-(3,4-Dichlorophenyl)-1-cyclohexylmethyl-5-formylmethyl-3-oxapiperidin-2-one

Product 1

HCID 677110605-(3,4-Dichlorophenyl)-1-(cyclohexylmethyl)-5-[2-(3-morpholinoazetidin-1-yl]ethyl)-3-oxapiperidin-2-oneYield 74.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Triethylamine (0.14 ml, 1 mmol) was added to a solution of 5-(3,4-dichlorophenyl)-1-cyclohexylmethyl-5-formylmethyl-3-oxapiperidin-2-one (see Preparation 1) (177 mg, 0.46 mmol) and 3-morpholinoazetidine dihydrochloride (119 mg, 0.54 mmol) in tetrahydrofuran (10 ml). After one hour, sodium triacetoxyborohydride (136 mg, 1.4 mol equivalent) was added, followed immediately by glacial acetic acid (26 μl, 1 equivalent) and the mixture stirred for 11/2 hours. Saturated aqueous sodium bicarbonate solution (10 ml) was added and the mixture extracted with ethyl acetate (10 ml×2). The combined organic extracts were dried over magnesium sulphate and the solvent removed under reduced pressure. The residue was chromatographed using silica gel eluting with a solvent gradient of methanol:ethylacetate (1:10 to 40:60 by volume) to provide the title compound (174 mg). LRMS m/z=509 (M+). TLC Rf=0.2 (silica, ethyl acetate:methanol, 9:1 by volume). Found: C,58.24; H,7.02, N,7.48. C26H37N3O3Cl2. 0.4 CH2Cl2 requires C,58.24, H,7.00, N,7.72%. 1H-NMR (CDCl3): δ=0.75-1.35(m,5H), 1.4-1 .5(m,1H), 1.5-1.9(m,7H), 2.1-2.4(m,6H), 2.7-2.8(m,2H), 2.8-3.0(m,1H), 3.05-3.3(m,2H), 3.3-3.55(m,4H), 3.6-3.8(m,4H), 4.3-4.4(m,1H), 4.5-4.6(m,1H), 7.0-7.1 (m,1H), 7.25-7.3(m,1H), 7.35-7.45(m,1H)ppm.

Workup

  1. extractionthe mixture extracted with ethyl acetate (10 ml×2)
  2. dry with materialThe combined organic extracts were dried over magnesium sulphate
  3. customthe solvent removed under reduced pressure
  4. customThe residue was chromatographed

Sources & evidence

ORD record
ord-ea749e0bed4c417f9156d06f382c5b85
Source dataset
uspto-grants-1998_12
Patent number
US05846965

Reaction notes

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