Monomethyl terephthalate → methyl 4-{[3-({(tert-butoxycarbonyl)[(1R)-1-(1-naphthyl)ethyl]amino}methyl)-4-phenylpiperidin-1-yl]carbonyl}benzoate

HRID 1691755Notes

Reaction equation

HRID 1691755 reaction equation
[C:1]([O:5][C:6](=[O:33])[N:7]([C@@H:21]([C:23]1[C:32]2[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=2)[CH:26]=[CH:25][CH:24]=1)[CH3:22])[CH2:8][CH:9]1[CH:14]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH2:13][CH2:12][NH:11][CH2:10]1)([CH3:4])([CH3:3])[CH3:2].[CH3:34][O:35][C:36]([C:38]1[CH:46]=[CH:45][C:41]([C:42](O)=[O:43])=[CH:40][CH:39]=1)=[O:37].C1C=CC2N(O)N=NC=2C=1.N=C=N.C(=O)([O-])[O-].[N-]=C=O>CN(C=O)C>[C:1]([O:5][C:6]([N:7]([CH2:8][CH:9]1[CH:14]([C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=2)[CH2:13][CH2:12][N:11]([C:42]([C:41]2[CH:45]=[CH:46][C:38]([C:36]([O:35][CH3:34])=[O:37])=[CH:39][CH:40]=2)=[O:43])[CH2:10]1)[C@@H:21]([C:23]1[C:32]2[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=2)[CH:26]=[CH:25][CH:24]=1)[CH3:22])=[O:33])([CH3:2])([CH3:3])[CH3:4]

Participants

8

Reactant 6

HCID 15513Monomethyl terephthalateHCID 19660Carbonate IonHCID 757711-HydroxybenzotriazoleHCID 105034IsocyanateHCID 160435CarbodiimideHCID 59178636tert-butyl[(1R)-1-(1-naphthyl)ethyl][(4-phenylpiperidin-3-yl)methyl]carbamate

Product 1

HCID 66906300methyl 4-{[3-({(tert-butoxycarbonyl)[(1R)-1-(1-naphthyl)ethyl]amino}methyl)-4-phenylpiperidin-1-yl]carbonyl}benzoate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a mixture of 13.3 mg of tert-butyl[(1R)-1-(1-naphthyl)ethyl][(4-phenylpiperidin-3-yl)methyl]carbamate, 6.3 mg of 4-methoxycarbonyl benzoic acid, 4.7 mg of HOBt, and 1 mL of DMF was added 100 mg of PS-Carbodiimide (Argonaut Technologies, USA) at room temperature, followed by stirring overnight. To the reaction mixture was added 50 mg of MP-Carbonate (Argonaut Technologies, USA), 50 mg of PS-Isocyanate (Argonaut Technologies, USA), and 0.5 mL of DMF at room temperature, followed by stirring for 4 hours, and the reaction mixture was filtered. The filtrate was concentrated under reduced pressure to obtain methyl 4-{[3-({(tert-butoxycarbonyl)[(1R)-1-(1-naphthyl)ethyl]amino}methyl)-4-phenylpiperidin-1-yl]carbonyl}benzoate as a crude product. To a solution of the obtained crude product in 0.5 mL of 1,4-dioxane solution was added 0.5 mL of a 4 M hydrogen chloride/ethyl acetate solution at room temperature, followed by stirring overnight. The reaction mixture was concentrated under reduced pressure to obtain methyl 4-{[3-({[(1R)-1-(1-naphthyl)ethyl]amino}methyl)-4-phenylpiperidin-1-yl]carbonyl}benzoate as a crude product. To a solution of the obtained crude product in 0.5 mL of THF were added 0.5 mL of methanol and 0.5 mL of a 1 M aqueous sodium hydroxide solution at room temperature, followed by stirring overnight. To the reaction mixture was added 0.5 mL of 1 M hydrochloric acid, followed by concentration under reduced pressure. The obtained residue was purified by separation using preparative high performance liquid chromatography (column: registered trademark SunFire, Waters, particle diameter of 5 μm, inner diameter of 19 mm, and length of 100 mm), flow rate: 25 ml/min., column temperature: 20° C., methanol—a 0.1% aqueous formic acid solution) to obtain 8.4 mg of 4-{[3-({[(1R)-1-(1-naphthyl)ethyl]amino}methyl)-4-phenylpiperidin-1-yl]carbonyl}benzoic acid.

Workup

  1. stirringby stirring for 4 hours
  2. filtrationthe reaction mixture was filtered
  3. concentrationThe filtrate was concentrated under reduced pressure

Sources & evidence

ORD record
ord-7f273d013dc548c2bacc1c6bb73f4300
Source dataset
uspto-grants-2012_04
Patent number
US08153658B2

Reaction notes

Loading…