Chlorosuccinimide → HCID 66727923, compound

HRID 1961549Notes

Reaction equation

HRID 1961549 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:11][CH:10]([C:12]2[CH:17]=[CH:16][C:15]([CH:18]=[N:19][OH:20])=[CH:14][CH:13]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C1C(=O)N(Cl)C(=O)C1.C(=O)([O-])O.[K+].[Cl:34][C:35]1[CH:40]=[C:39]([C:41]([C:43]([F:46])([F:45])[F:44])=[CH2:42])[CH:38]=[C:37]([Cl:47])[CH:36]=1>CN(C=O)C.ClCCl.CCCCCC.C(OCC)(=O)C.CO>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH:10]([C:12]2[CH:13]=[CH:14][C:15]([C:18]3[CH2:42][C:41]([C:39]4[CH:38]=[C:37]([Cl:47])[CH:36]=[C:35]([Cl:34])[CH:40]=4)([C:43]([F:44])([F:46])[F:45])[O:20][N:19]=3)=[CH:16][CH:17]=2)[CH2:11]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

10

Reactant 4

HCID 31398ChlorosuccinimideHCID 516893Potassium BicarbonateHCID 231598231,3-Dichloro-5-(3,3,3-trifluoroprop-1-en-2-yl)benzeneHCID 766614793-[4-(Hydroxyimino-methyl)-phenyl]-azetidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 66727923HCID 66727923, compound

Reagents, catalysts & solvents 5

HCID 887MethanolSolventHCID 6228DimethylformamideSolvent2×HCID 6344DichloromethaneSolventHCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

To a stirred solution of 3-[4-(Hydroxyimino-methyl)-phenyl]-azetidine-1-carboxylic acid tert-butyl ester (Preparation 39, 1 g, 3.62 mmol, 1.0 equivalents) in DMF (6.0 mL) was added NCS (725.26 mg, 5.43 mmol, 1.5 equivalents) and heated to 50° C. for 1 hour. Progress of the reaction was monitored by TLC using 5% methanol in dichloromethane. After complete consumption of starting material, reaction was cooled to 0° C. followed by the addition of potassium hydrogen carbonate (543.18 mg, 5.43 mmol, 1.5 equivalents) and pre-dissolved solution of 1,3-Dichloro-5-(1-trifluoromethyl-vinyl)-benzene (1.04 g, 4.345 mmol, 1.2 equivalents) in DMF (4.0 mL). Resulting reaction was stirred at room temperature for 16 hours under nitrogen atmosphere. Progress of the reaction was monitored by TLC using 20% ethyl acetate in hexane and visualized in UV light (254 nm). Reference of required product was 0.6 and 0.5 for starting material. After consumption of starting material, reaction mixture was quenched with water (40 mL) extracted with diethyl ether (3×50 mL). Combined organic layer was washed with brine (20 mL) and dried over anhydrous sodium sulphate and concentrated in vacuo to afford (1.50 g, crude). Further purification by column chromatography (on neutral alumina) using 10% ethyl acetate in hexane as eluent afforded off white solid 1.3 g (69.84%). 1H NMR and LC-MS were consistent. 1H NMR (400 MHz, DMSO-d6) δ 1.39 (s, 9H), 3.84 (m, 3H), 4.25-4.38 (m, 4H), 7.47 (d, J=8 Hz, 2H), 7.62 (d, J=1 Hz, 2H), 7.71 (d, J=8 Hz, 2H), 7.81 (t, J=2 Hz, 1H). LC-MS (m/z):=513 (M−H).

Workup

  1. customAfter complete consumption of starting material, reaction
  2. temperaturewas cooled to 0° C.
  3. customResulting
  4. customreaction

Sources & evidence

ORD record
ord-72f42ce857784ca5808e5eb910756e2b
Source dataset
uspto-grants-2013_04
Patent number
US08415310B2

Reaction notes

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