Trifluoroacetic acid → 1'-(2,2,2-trifluoroacetyl)spiro[indene-1,4'-piperidin]-3(2H)-one

HRID 2192223Notes

Reaction equation

HRID 2192223 reaction equation
[C:1](O)([C:3]([F:6])([F:5])[F:4])=[O:2].[O:8]=[C:9]1[C:29]2[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=2)[C:11]2([CH2:16][CH2:15][N:14](C(OC(C)(C)C)=O)[CH2:13][CH2:12]2)[CH2:10]1.C(N(CC)CC)C.FC(F)(F)C(OC(=O)C(F)(F)F)=O>ClCCl.CN(C1C=CN=CC=1)C>[F:4][C:3]([F:6])([F:5])[C:1]([N:14]1[CH2:15][CH2:16][C:11]2([C:24]3[C:29](=[CH:28][CH:27]=[CH:26][CH:25]=3)[C:9](=[O:8])[CH2:10]2)[CH2:12][CH2:13]1)=[O:2]

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 9845Trifluoroacetic anhydrideHCID 18673579Tert-butyl 3-oxo-2,3-dihydrospiro[indene-1,4'-piperidine]-1'-carboxylate

Product 1

HCID 193669921'-(2,2,2-trifluoroacetyl)spiro[indene-1,4'-piperidin]-3(2H)-oneYield 92%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×

Procedure

TFA (25 mL) was added to a solution of commercially available tert-butyl 3-oxo-2,3-dihydrospiro[indene-1,4′-piperidine]-1′-carboxylate (5.0 g, 16.6 mmol) in dichloromethane (25 mL) at 0° C. The reaction was then allowed to warm to rt for 30 min. The reaction was evaporated and dried under high vacuum for 30 min. The crude amine was dissolved in dichloromethane (25 mL) and triethylamine (6.9 mL, 49.8 mmol), trifluoroacetic anhydride (2.6 mL, 18.3 mmol) and DMAP (20 mg, 0.17 mmol) were added in that order. The reaction was stirred at rt for 2 h and then diluted in dichloromethane and washed with water, sat. NH4Cl solution and brine. The organics were then dried (MgSO4), filtered and evaporated to give 19a as a light yellow solid (4.55 g, 92%). (M+H)+=298. 1H NMR (400 MHz, CDCl3) δ ppm 7.75 (d, J=7.6 Hz, 1H); 7.66 (t, J=7.0 Hz, 1H); 7.48 (d, J=7.9 Hz, 1H); 7.44 (t, J=7.5 Hz, 1H); 4.69 (d, J=15.9 Hz, 1H); 4.13 (d, J=14.1 Hz, 1H); 3.30 (t, J=11.8 Hz, 1H); 2.90 (t, J=13.4 Hz, 1H); 2.68 (m, 2H); 2.05 (dt, J=13.6, 3.8 Hz, 2H); 1.66 (d, J=13.9 Hz, 2H).

Workup

  1. customThe reaction was evaporated
  2. customdried under high vacuum for 30 min
  3. dissolutionThe crude amine was dissolved in dichloromethane (25 mL)
  4. washwashed with water, sat. NH4Cl solution and brine
  5. dry with materialThe organics were then dried (MgSO4)
  6. filtrationfiltered
  7. customevaporated

Sources & evidence

ORD record
ord-803fa02cfedc4aafbbf22e7675f667a0
Source dataset
uspto-grants-2012_12
Patent number
US08329718B2

Reaction notes

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