Trifluoroacetic acid → HCID 69619565, compound

HRID 1791374Notes

Reaction equation

HRID 1791374 reaction equation
C(OC(N1CCC(C)CC1C(O)=O)=O)(C)(C)C.C(N(CC)CC)C.ClC(OCC(C)C)=O.ClC1C=C(C=CC=1)C(NO)=N.[C:44]([O:48][C:49]([N:51]1[CH2:56][CH2:55][CH:54]([CH3:57])[CH2:53][CH:52]1[C:58]1[O:62][N:61]=[C:60]([C:63]2[CH:68]=[CH:67][CH:66]=[C:65]([Cl:69])[CH:64]=2)[N:59]=1)=[O:50])([CH3:47])([CH3:46])[CH3:45].FC(F)(F)C(O)=O>C1COCC1.CN(C=O)C.ClCCl>[C:44]([O:48][C:49]([N:51]1[CH2:56][CH2:55][CH:54]([CH3:57])[CH2:53][CH:52]1[C:58]1[O:62][N:61]=[C:60]([C:63]2[CH:68]=[CH:67][CH:66]=[C:65]([Cl:69])[CH:64]=2)[N:59]=1)=[O:50])([CH3:45])([CH3:46])[CH3:47].[Cl:69][C:65]1[CH:64]=[C:63]([C:60]2[N:59]=[C:58]([C@H:52]3[CH2:53][C@H:54]([CH3:57])[CH2:55][CH2:56][NH:51]3)[O:62][N:61]=2)[CH:68]=[CH:67][CH:66]=1

Participants

11

Reactant 6

HCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 62365Isobutyl chloroformateHCID 144823891-(tert-Butoxycarbonyl)-4-methylpiperidine-2-carboxylic acidHCID 69619328HCID 69619328, compoundHCID 178513296HCID 178513296, compound

Product 2

HCID 69619328HCID 69619328, compoundYield 33.9%HCID 69619565HCID 69619565, compoundYield 70%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
130 °C

Procedure

2-[3-(3-Chloro-phenyl)-[1,2,4]oxadiazol-5-yl]-4-methyl-piperidine-1-carboxylic acid tert-butyl ester (320 mg, 33.9%) was prepared according to the procedure in Example 25 from 4-methyl-piperidine-1,2-dicarboxylic acid 1-tert-butyl ester (607.5 mg, 2.5 mmol), triethylamine (1.01 g, 10 mmol) with isobutyl chloroformate (348 mg, 2.55 mmol) in THF (5 mL). After 30 minutes, 3-Chloro-N-hydroxy-benzamidine (425 mg, 2.5 mmol) in DMF (4 mL) was added and the mixture was heated to 130° C. for 4 h. The product was purified by column chromatography with 10% ethyl acetate in hexanes. Deprotection was carried out according to the procedure in Example 39 from 2-[3-(3-chloro-phenyl)-[1,2,4]oxadiazol-5-yl]-4-methyl-piperidine-1-carboxylic acid tert-butyl ester(320 mg, 0.847 mmol) with trifluoroacetic acid (1.3 ml) and dichloromethane(10 mL) for 3 h. Purification by column chromatography with 50/50 ethyl acetate/hexanes gave trans-2-[3-(3-chloro-phenyl)-[1,2,4]oxadiazol-5-yl]-4-methyl-piperidine 164.8 mg (70%); 1H-NMR(CDCl3) 6(ppm): 8.10 (s, 1H), 7.97 (d, 1H), 7.42 (m, 2H), 4.07 (d, 1H), 3.26 (dd, 1H), 2.80 (t, 1H), 2.17 (d, 1H), 1.99 (w, 1H), 1.69 (m, 2H), 1.24 (m, 2H) and 1.02 (d, 3H), and cis-2-[3-(3-chloro-phenyl)-[1,2,4]oxadiazol-5-yl]-4-methyl-piperidine 23.9 mg(10.2%); 1H-NMR(CDCl3) 8(ppm): 8.10 (s, 1H), 7.97 (d, 1H), 7.43 (m, 2H), 4.45 (t, 1H), 2.93 (m, 2H), 2.24(m, 2H), 2.68 (m, 3H), 1.29 (m, 1H) and 0.99 (d, 3H).

Workup

  1. customThe product was purified by column chromatography with 10% ethyl acetate in hexanes
  2. customPurification by column chromatography with 50/50 ethyl acetate/hexanes

Sources & evidence

ORD record
ord-1c91f3cf7b3e433fb4bee9e1b9f6d676
Source dataset
uspto-grants-2006_07
Patent number
US07074809B2

Reaction notes

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