(2S)-1-((tert-butoxy)carbonyl)piperidine-2-carboxylic acid → 1-[(Tert-butoxy)carbonyl]piperidine-2-carboxylic acid

HRID 1978895Notes

Reaction equation

HRID 1978895 reaction equation
[CH3:1][C:2]([O:5][C:6]([N:8]1[C@H:13]([C:14]([OH:16])=[O:15])[CH2:12][CH2:11][CH2:10][CH2:9]1)=[O:7])([CH3:4])[CH3:3].CCN=C=NCCCN(C)C.Cl>CN(C)C1C=CN=CC=1.C(#N)C>[C:6]([N:8]1[CH2:9][CH2:10][CH2:11][CH2:12][CH:13]1[C:14]([OH:16])=[O:15])([O:5][C:2]([CH3:4])([CH3:3])[CH3:1])=[O:7]

Participants

5

Reactant 2

HCID 688617(2S)-1-((tert-butoxy)carbonyl)piperidine-2-carboxylic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride

Product 1

HCID 5818311-[(Tert-butoxy)carbonyl]piperidine-2-carboxylic acidYield 85%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6342AcetonitrileSolvent

Procedure

N-Boc-L-pipecolic acid (0.280 g, 1.22 mmol) was esterified with 1-phenyl-7-(3′-pyridyl)-heptan-4-ol (0.394 g, 1.46 mmol) employing EDC hydrochloride (0.350 g, 1.83 mmol) and 4-dimethylaminopyridine (0.081 g, 0.663 mmol) in acetonitrile (25 mL). Purification by silica gel chromatography, eluting with chloroform/methanol (100:0 to 99:1), gave the pure 1-phenyl-7-(3′-pyridyl)-heptan-4-ol ester of N-Boc-pipecolic acid in 85% yield (0.498 g) as a colorless oil. MS: M+H=481. LC-MS: System 2 (4 min gradient), tR=3.8 min. A portion of this N-Boc ester (0.369 g, 0.768 mmol) was deprotected as described in example 1 with trifluoroacetic acid. The crude product was then coupled with α,α-difluoro-3,4,5-trimethoxyphenylacetic acid (0.241 g, 0.921 mmol), using EDC hydrochloride (0.220 g, 1.15 mmol) and 4-dimethylaminopyridine (0.101 g, 0.826 mmol) in acetonitrile (25 mL). After extractive work up as described in example 1, the product was purified by silica gel chromatography, eluting with hexane/ethyl acetate (4:1 to 1:1), to give the title compound (0.624 g, 1.05 mmol, 78%) as a pale yellow oil. MS: M+H=625. 1H-NMR: 8.38-8.34 (m, 2H), 7.75-7.00 (m, 7H), 6.76-6.63 (m & s, 2H), 5.25-4.10 (4×m, 2H), 3.80-3.50 (m, 10H), 3.00-2.85 (m, 1H), 2.52 (m, 2H), 2.25-1.00 (4×m, 16H). LC-MS: System 2 (4 min gradient), tR, for the diastereomers=3.6 and 3.8 min. Anal. C35H42N2O6F2, C=67.40; H =6.85; N=4.23; F=5.86; (found) C=67.29; H=6.78; N=4.48; F=6.08; (calcd.).

Workup

  1. customPurification by silica gel chromatography
  2. washeluting with chloroform/methanol (100:0 to 99:1)

Sources & evidence

ORD record
ord-6aea391f692d440593d3aa444cd560f1
Source dataset
uspto-grants-2001_05
Patent number
US06239146B1

Reaction notes

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