2-(2,4-Difluoro-phenyl)-6-methoxy-naphthalene-1-carbaldehyde → HCID 11192515, compound

HRID 1513974Notes

Reaction equation

HRID 1513974 reaction equation
[C:1]([O:5][C:6](=[O:23])[N:7]([C:16]1[CH:21]=[CH:20][C:19](Br)=[CH:18][CH:17]=1)[CH2:8][CH2:9][N:10]1[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]1)([CH3:4])([CH3:3])[CH3:2].C([Li])CCC.F[C:30]1[CH:35]=[C:34]([F:36])[CH:33]=[CH:32][C:31]=1[C:37]1[CH:46]=[CH:45][C:44]2[C:39](=[CH:40][CH:41]=[C:42]([O:47][CH3:48])[CH:43]=2)[C:38]=1[CH:49]=[O:50]>O1CCCC1.ClCCl.[Cl-].[NH4+]>[C:1]([O:5][C:6](=[O:23])[N:7]([C:16]1[CH:21]=[CH:20][C:19]([CH:49]2[O:50][C:30]3[C:31](=[CH:32][CH:33]=[C:34]([F:36])[CH:35]=3)[C:37]3[C:38]2=[C:39]2[C:44](=[CH:45][CH:46]=3)[CH:43]=[C:42]([O:47][CH3:48])[CH:41]=[CH:40]2)=[CH:18][CH:17]=1)[CH2:8][CH2:9][N:10]1[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]1)([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 3

HCID 575525532-(2,4-Difluoro-phenyl)-6-methoxy-naphthalene-1-carbaldehydeHCID 57552562HCID 57552562, compoundHCID 178418339Butyllithium

Product 1

HCID 11192515HCID 11192515, compoundYield 92%

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolventHCID 25517Ammonium ChlorideSolvent

Conditions

Temperature
-78 °C

Procedure

Dissolve (4-bromo-phenyl)-(2-piperidin-1-yl-ethyl)-carbamic acid tert-butyl ester in dry tetrahydrofuran (20 mL). Cool to −78° C. and add 1.6 M n-butyl lithium in hexanes (0.79 mL). After 30 minutes, add 2-(2,4-difluoro-phenyl)-6-methoxy-naphthalene-1-carbaldehyde (0.25 g, 0.839 mmol) and stir 45 minutes cold. Warm to room temperature over 1 hour. Reflux 2 hrs. Cool to room temperature and dilute with dichloromethane (20 mL) and saturated aqueous ammonium chloride (20 mL). Separate the organic layer and wash the aqueous layer twice with dichloromethane. Combine the organics and dry over magnesium sulfate. Filter and concentrate in vacuo. Purify the residue by column chromatography using a silica gel column eluting with a linear gradient beginning with dichloromethane and ending with 4:1 dichloromethane methanol to give 0.45 g (92%) of the title compound: mass spectrum (ion spray) m/z=583.3 (M+H).

Workup

  1. temperatureWarm to room temperature over 1 hour
  2. temperatureReflux 2 hrs
  3. temperatureCool to room temperature
  4. customSeparate the organic layer
  5. washwash the aqueous layer twice with dichloromethane
  6. dry with materialdry over magnesium sulfate
  7. filtrationFilter
  8. concentrationconcentrate in vacuo
  9. customPurify the residue by column chromatography
  10. washeluting with a linear gradient

Sources & evidence

ORD record
ord-50614d7d21894101a862788253974c88
Source dataset
uspto-grants-2012_07
Patent number
US08217032B2

Reaction notes

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