1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine) → 4-[2-(1-tert-Butoxycarbonyl-piperidin-4-yl)-2,3-dihydro-furo[2,3-c]pyridin-5-yl]-piperazine-1-carboxylic acid benzyl ester

HRID 1184719Notes

Reaction equation

HRID 1184719 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]2(C)[O:23][C:17]3=[CH:18][N:19]=[C:20](Cl)[CH:21]=[C:16]3[CH2:15]2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH2:25]([O:32][C:33]([N:35]1[CH2:40][CH2:39][NH:38][CH2:37][CH2:36]1)=[O:34])[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.CC([O-])(C)C.[K+]>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH2:25]([O:32][C:33]([N:35]1[CH2:40][CH2:39][N:38]([C:20]2[CH:21]=[C:16]3[CH2:15][CH:14]([CH:11]4[CH2:10][CH2:9][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[CH2:13][CH2:12]4)[O:23][C:17]3=[CH:18][N:19]=2)[CH2:37][CH2:36]1)=[O:34])[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1

Participants

7

Reactant 4

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 643495Benzyl piperazine-1-carboxylateHCID 23665647Potassium tert-butoxideHCID 866749014-(5-Chloro-2-methyl-2,3-dihydrofuro[2,3-c]pyridin-2-yl)piperidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 679738584-[2-(1-tert-Butoxycarbonyl-piperidin-4-yl)-2,3-dihydro-furo[2,3-c]pyridin-5-yl]-piperazine-1-carboxylic acid benzyl ester

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
105 °C

Procedure

4-(5-Chloro-2-methyl-2,3-dihydro-furo[2,3-c]pyridin-2-yl)-piperidine-1-carboxylic acid tert-butyl ester (530 mg) is added to a mixture of piperazine-1-carboxylic acid benzyl ester (460 μL), Pd2(dba)3 (360 mg), Xantphos (700 mg), and potassium tert-butylate (270 mg) in toluene (16 mL) under an argon atmosphere. The reaction mixture is stirred in an oil bath at 105° C. for 4 h. The reaction mixture is concentrated in vacuo and chromatographed on silica gel (cyclohexane/ethyl acetate 70:30→35:65) to give the title compound. LC (method 10): tR=1.68 min; Mass spectrum (ESI+): m/z=523 [M+H]+.

Workup

  1. concentrationThe reaction mixture is concentrated in vacuo
  2. customchromatographed on silica gel (cyclohexane/ethyl acetate 70:30→35:65)

Sources & evidence

ORD record
ord-1301561c29274c78bd85a71df0166196
Source dataset
uspto-grants-2014_03
Patent number
US08669271B2

Reaction notes

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