Triethylamine → HCID 57878582, compound

HRID 887954Notes

Reaction equation

HRID 887954 reaction equation
[F:1][C:2]([F:14])([F:13])[C:3]1[CH:4]=[C:5]([S:9](Cl)(=[O:11])=[O:10])[CH:6]=[CH:7][CH:8]=1.[C:15]([O:19][C:20]([N:22]1[CH2:27][CH2:26][CH2:25][CH:24]([NH:28][CH:29]2[CH2:31][CH2:30]2)[CH2:23]1)=[O:21])([CH3:18])([CH3:17])[CH3:16].C(N(CC)CC)C>ClCCl>[C:15]([O:19][C:20]([N:22]1[CH2:27][CH2:26][CH2:25][CH:24]([N:28]([CH:29]2[CH2:30][CH2:31]2)[S:9]([C:5]2[CH:6]=[CH:7][CH:8]=[C:3]([C:2]([F:14])([F:13])[F:1])[CH:4]=2)(=[O:11])=[O:10])[CH2:23]1)=[O:21])([CH3:18])([CH3:16])[CH3:17]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 27332503-(Trifluoromethyl)benzenesulfonyl chlorideHCID 50986436tert-Butyl 3-(cyclopropylamino)piperidine-1-carboxylate

Product 1

HCID 57878582HCID 57878582, compoundYield 45%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
37 °C

Procedure

3-Trifluoromethylphenylsulfonyl chloride (4) (12 g, 49 mmol, Aldrich) was added to a mixture of the crude compound 3, triethylamine (TEA, 10 mL) and dichloromethane (DCM, 10 mL) at room temperature. The resulting mixture was heated and stirred at 37° C. for 2 days. The reaction mixture was cooled to room temperature, washed with water (10 mL) and then with brine, and concentrated and purified by column (silica gel) eluting with EtOAc/hexanes (3/7) to afford 3-[N-cyclopropyl-N-(3-trifluoromethylbenzenesulfonyl)amino]piperidine-1-carboxylic acid tert-butyl ester (5) as a sticky oil (10 g, yield 45% in two steps), which was dissolved in 100 mL of 1,4-dioxane. HCl (10 mL, concentrated aq.) was added to the 1,4-dioxane solution at room temperature. The resulting mixture was stirred at room temperature for 48 hours, and concentrated under vacuum. The residue was washed with ethyl ether, and dried to obtain the desired title compound 6 as an oil (6.5 g, 81%). 1H NMR (400 MHz, CD3OD): δ 8.22 (d, j=7.9 Hz, 1H), 8.17 (s, 1H), 8.06 (d, j=7.8 Hz, 1H), 7.90 (d, 1H, j=7.8 Hz, 1H), 4.17-4.24 (m, 1H), 3.34-3.38 (m, 2H), 3.22-3.29 (m, 1H), 2.87-2.95 (m, 1H), 1.98-2.18 (m, 3H), 1.68-1.82 (m, 2H), 1.04-1.09 (m, 1H), 0.79-0.92 (m, 3H); LC: 100%; MS: m/z=349 (M+1).

Workup

  1. temperatureThe resulting mixture was heated
  2. temperatureThe reaction mixture was cooled to room temperature
  3. washwashed with water (10 mL)
  4. concentrationwith brine, and concentrated
  5. custompurified by column (silica gel)
  6. washeluting with EtOAc/hexanes (3/7)

Sources & evidence

ORD record
ord-f608a8a16c614d33b95faa08b0383561
Source dataset
uspto-grants-2012_08
Patent number
US08247442B2

Reaction notes

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