Trifluoroacetic acid → 1-(5-Chlorospiro[indoline-3,4'-piperidin]-1-yl)ethanone

HRID 706352Notes

Reaction equation

HRID 706352 reaction equation
FC(F)(F)C(O)=O.C(OC([N:15]1[CH2:20][CH2:19][C:18]2([C:28]3[C:23](=[CH:24][CH:25]=[C:26]([Cl:29])[CH:27]=3)[N:22]([C:30](=[O:32])[CH3:31])[CH2:21]2)[CH2:17][CH2:16]1)=O)(C)(C)C.CO.ClCCl.C(N(CC)CC)C>ClCCl>[C:30]([N:22]1[C:23]2[C:28](=[CH:27][C:26]([Cl:29])=[CH:25][CH:24]=2)[C:18]2([CH2:19][CH2:20][NH:15][CH2:16][CH2:17]2)[CH2:21]1)(=[O:32])[CH3:31]

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 21913430dichloromethane MeOH Et3NHCID 58046557tert-Butyl 1-acetyl-5-chlorospiro[indoline-3,4'-piperidine]-1'-carboxylate

Product 1

HCID 573199971-(5-Chlorospiro[indoline-3,4'-piperidin]-1-yl)ethanoneYield 96.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Trifluoroacetic acid (25 ml) was added to a stirred solution of 1-acetyl-5-chlorospiro[indoline-3,4′-piperidine]-1′-carboxylic acid tert-butyl ester (8 g) in anhydrous dichloromethane (250 ml) under an atmosphere of nitrogen. The reaction was left as such for 3 h. The reaction was washed with saturated bicarbonate solution (200 ml) and dried over sodium sulphate and concentrated in vacuo to yield an off white solid. Flash chromatography [SiO2: methanol-dichloromethane-triethylamine (90:5:5)] yielded 5.6 g (61%) of the desired 1-Acetyl-5-chlorospiro[indoline-3,4′-piperidine]. 1H NMR (400 MHz, CDCl3) δ 6:1 mixture of rotamers. Major rotamer 1.70 (m, 2H), 1.80 (m, 2H), 2.27 (s, 3H), 2.75 (t, J=12 Hz, 2H), 3.15 (m, 2H), 3.90 (s, 2H), 7.12 (d, J=1 Hz, 1H), 7.18 (dd, J=7 & 1 Hz, 1H), 8.15 (d, J=7 Hz, 1H). Minor rotamer (partial data) 2.44 (s, 3H), 2.86 (m, 2H), 3.10 (m, 2H), 4.05 (s, 2H). MS (ES+) 265/267 (M+H+).

Workup

  1. washThe reaction was washed with saturated bicarbonate solution (200 ml)
  2. dry with materialdried over sodium sulphate
  3. concentrationconcentrated in vacuo
  4. customto yield an off white solid

Sources & evidence

ORD record
ord-85da83f406c64a469634755ac4e37f9e
Source dataset
uspto-grants-2015_11
Patent number
US09174987B2

Reaction notes

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