Diisopropylethylamine → 1-Acetyl-5-chloro-1'-[trans-3-(4-chlorophenyl)allyl]spiro[indoline-3,4'-piperidine]

HRID 706353Notes

Reaction equation

[Cl:1][C:2]1[CH:11]=[CH:10][C:5]([CH:6]=[CH:7][CH2:8]Cl)=[CH:4][CH:3]=1.[C:12]([N:15]1[C:28]2[C:23](=[CH:24][C:25]([Cl:29])=[CH:26][CH:27]=2)[C:17]2([CH2:22][CH2:21][NH:20][CH2:19][CH2:18]2)[CH2:16]1)(=[O:14])[CH3:13].C(N(C(C)C)CC)(C)C.C(OCC)(=O)C.CCCCCC.C(N(CC)CC)C>C(Cl)(Cl)Cl>[C:12]([N:15]1[C:28]2[C:23](=[CH:24][C:25]([Cl:29])=[CH:26][CH:27]=2)[C:17]2([CH2:22][CH2:21][N:20]([CH2:8]/[CH:7]=[CH:6]/[C:5]3[CH:10]=[CH:11][C:2]([Cl:1])=[CH:3][CH:4]=3)[CH2:19][CH2:18]2)[CH2:16]1)(=[O:14])[CH3:13]

Participants

Conditions

Temperature: 50 °C

Procedure

A solution of 4-chlorocinnamyl chloride (4.0 g) in chloroform (120 ml) was added slowly to a stirred mixture of 1-acetyl-5-chlorospiro[indoline-3,4′-piperidine] (5.3 g) and diisopropylethylamine (6.7 ml) in chloroform (120 ml) under an atmosphere of nitrogen at room. The reaction was heated to 50° C. for 30 h. The reaction mixture was concentrated in vacuo to yield a red oil. Flash chromatography [SiO2; ethyl acetate-hexane-triethylamine (50:50:1)] yielded 5.1 g (68%) of the desired compound. 1H NMR (400 MHz, CDCl3) δ 5:1 mixture of rotamers. Major rotamer 1.70 (d, J=12 Hz, 2H), 2.0 (td, J=12 & 2 Hz), 2.08 (t, J=12 Hz, 2H), 2.25 (s, 3H), 3.03 (d, J=12 Hz, 2H), 3.20 (d, J=7 Hz, 2H), 3.96 (s, 2H), 6.28 (dt, J=12 & 5 Hz, 1H), 6.50 (d, J=12 Hz, 1H), 7.13 (d, J=1 Hz, 1H), 7.18 (dd, J=7 & 1 Hz, 1H), 7.3 (m, 4H), 8.15 (d, J=7 Hz, 1H). Minor rotamer (partial data) 2.42 (s, 3H), 4.00 (s, 2H). MS (ES+) 415/417/419 (M+H+).

Workup

concentrationThe reaction mixture was concentrated in vacuo
customto yield a red oil

Sources & evidence

ORD record: ord-b7ef12254e604bc08a15c4f9c54a59aa
Source dataset: uspto-grants-2015_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09174987B2

Reaction notes

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