Triethylamine → 4-[4-(1,3,3-Trimethyl-6-aza-bicyclo[3.2.1]octane-6-carbonyl)-thiophen-2-yl]-piperidine-1 carboxylic acid tert-butyl ester

HRID 1809106Notes

Reaction equation

HRID 1809106 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[S:15][CH:16]=[C:17]([C:19](O)=[O:20])[CH:18]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.[CH3:29][C:30]12[CH2:37][CH:34]([NH:35][CH2:36]1)[CH2:33][C:32]([CH3:39])([CH3:38])[CH2:31]2.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C(#N)C>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][CH:11]([C:14]2[S:15][CH:16]=[C:17]([C:19]([N:35]3[CH2:36][C:30]4([CH3:29])[CH2:37][CH:34]3[CH2:33][C:32]([CH3:39])([CH3:38])[CH2:31]4)=[O:20])[CH:18]=2)[CH2:12][CH2:13]1)=[O:7])([CH3:3])([CH3:2])[CH3:4]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 1037871,3,3-Trimethyl-6-azabicyclo(3.2.1)octaneHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 595424805-(1-(Tert-butoxycarbonyl)piperidin-4-yl)thiophene-3-carboxylic acid

Product 1

HCID 595425534-[4-(1,3,3-Trimethyl-6-aza-bicyclo[3.2.1]octane-6-carbonyl)-thiophen-2-yl]-piperidine-1 carboxylic acid tert-butyl esterYield 92.4%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

4-(4-Carboxy-thiophen-2-yl)-piperidine-1-carboxylic acid t-butyl ester (0.1 g, 0.32 mmol) was dissolved in acetonitrile (2 mL). Triethylamine (0.96 mmol), 1,3,3-trimethyl-6-aza-bicyclo[3.2.1]octane (0.35 mmol) and HATU (0.35 mmol) were added and the reaction stirred at room temperature for 18 hours. The solvent was evaporated and the residue was purified by flash chromatography, eluting with 0-50% ethyl acetate in cyclohexane. The fractions containing the desired product were concentrated under vacuum to give the title compound (0.132 g). 1H NMR (400 MHz, CHCl3-d; 80° C.); □ 7.6 (s, 1H), 7.0 (s, 1H), 4.3 (m, 1H), 4.0 (m, 2H), 3.4 (m, 1H), 3.2 (m, 1H), 3.0 (m, 1H), 2.9 (m, 1.9 (m, 2H), 1.7 (m, 1H), 1.6-0.9 (m, 26H).

Workup

  1. customThe solvent was evaporated
  2. customthe residue was purified by flash chromatography
  3. washeluting with 0-50% ethyl acetate in cyclohexane
  4. additionThe fractions containing the desired product
  5. concentrationwere concentrated under vacuum

Sources & evidence

ORD record
ord-108851e33f9c4a8aa57dd99909e5938b
Source dataset
uspto-grants-2013_01
Patent number
US08362008B2

Reaction notes

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