Cyclohexyl isocyanide → HCID 178451555, compound

HRID 1641301Notes

Reaction equation

HRID 1641301 reaction equation
[C:1]([N:8]1[CH2:13][CH2:12][CH2:11][CH2:10][C:9]1=O)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[CH:15]1([N+:21]#[C-:22])[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]1.[N-:23]=[C:24]=[O:25].[K+].Cl.[F:28][C:29]1[CH:30]=[C:31]([CH:33]=[CH:34][CH:35]=1)[NH2:32]>O.C(Cl)Cl.CO>[CH:15]1([NH:21][C:22]2[C:11]3([CH2:12][CH2:13][N:8]([C:1]([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2])[CH2:9][CH2:10]3)[N:32]([C:31]3[CH:33]=[CH:34][CH:35]=[C:29]([F:28])[CH:30]=3)[C:24](=[O:25])[N:23]=2)[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]1

Participants

8

Reactant 4

HCID 79129Cyclohexyl isocyanideHCID 27557653-Fluorophenylamine hydrochlorideHCID 7577838tert-Butyl 2-oxopiperidine-1-carboxylateHCID 11051572Potassio isocyanate

Product 1

HCID 178451555HCID 178451555, compound

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To a 10 mL MeOH suspension of 4.05 g (20.3 mmol) N-boc piperidinone and 2.11 g (19.3 mmol) cyclohexyl isocyanide was added a solution of 2.06 g (25.4 mmol) potassium isocyanate in 2.8 mL H2O in one portion with stirring followed by 3.0 g (20.3 mmol) 3-fluoroaniline hydrochloride in portions over 5 m. After stirring for 2 h the reaction was treated with 250 ml CH2Cl2. The organic layer was washed with water (2×50 ml), brine (1×50 ml), dried over Na2SO4, filtered and concentrated to dryness in vacuo to give a crude oil (9.68 g). Purification by automated flash chromatography (0-5.5% MeOH in CH2Cl2 over 28 m) afforded tert-butyl 4-(cyclohexylamino)-1-(3-fluorophenyl)-2-oxo-1,3,8-triazaspiro[4.5]dec-3-ene-8-carboxylate as a white solid. 1H NMR (CDCl3, 400 MHz): δ 7.41 (m, 1H), 7.11 (m, 1H), 7.05 (d, J=7.88 Hz, 1H), 6.99 (m, 1H), 5.40 (br s, 1H), 4.02 (m, 1H), 3.58 (m, 2H), 3.27 (m, 2H), 2.05 (m, 4H), 1.92 (m, 2H), 1.71 (m, 4H), 1.44 (m, 12H), 1.24 (m, 2H). Electrospray mass spectrum: M+H=445.2

Workup

  1. stirringAfter stirring for 2 h the reaction
  2. washThe organic layer was washed with water (2×50 ml), brine (1×50 ml)
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated to dryness in vacuo
  6. customto give a crude oil (9.68 g)
  7. customPurification by automated flash chromatography (0-5.5% MeOH in CH2Cl2 over 28 m)

Sources & evidence

ORD record
ord-80455c0fc888462883df7fec3ec9006f
Source dataset
uspto-grants-2012_02
Patent number
US08114887B2

Reaction notes

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