Hydrochloric Acid → 1-(2-(4-(2-(5-Fluorothiophen-2-yl)-6-methoxynaphthalen-1-yloxy)phenoxy)ethyl)piperidine

HRID 445205Notes

Reaction equation

HRID 445205 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[C:9]([O:13][C:14]1[CH:28]=[CH:27][C:17]([O:18][CH2:19][CH2:20][N:21]3[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]3)=[CH:16][CH:15]=1)=[C:8]([C:29]1[S:30][CH:31]=[CH:32][CH:33]=1)[CH:7]=[CH:6]2.C([Li])CCC.C1C=CC(S(N(S(C2C=CC=CC=2)(=O)=O)[F:49])(=O)=O)=CC=1.Cl>O1CCCC1.CCOCC>[F:49][C:31]1[S:30][C:29]([C:8]2[CH:7]=[CH:6][C:5]3[C:10](=[CH:11][CH:12]=[C:3]([O:2][CH3:1])[CH:4]=3)[C:9]=2[O:13][C:14]2[CH:15]=[CH:16][C:17]([O:18][CH2:19][CH2:20][N:21]3[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]3)=[CH:27][CH:28]=2)=[CH:33][CH:32]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 588007N-FluorobenzenesulfonimideHCID 583385531-(2-(4-(6-Methoxy-2-(thiophen-2-yl)naphthalen-1-yloxy)phenoxy)ethyl)piperidineHCID 178418339Butyllithium

Product 1

HCID 583385431-(2-(4-(2-(5-Fluorothiophen-2-yl)-6-methoxynaphthalen-1-yloxy)phenoxy)ethyl)piperidineYield 25%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

Add 1-(2-(4-(6-methoxy-2-(thiophen-2-yl)naphthalen-1-yloxy)phenoxy)ethyl)piperidine (153 mg, 0.4 mmol) and tetrahydrofuran (3.3 mL) to a screw-cap vial under argon. Cool the resulting solution to −78° C. Add n-butyl lithium (1.6M in hexanes; 230 μL, 0.4 mmol) dropwise. Warm the resulting solution to 0° C. and stir for 30 min. Add a solution of N-fluorobenzenesulfonimide (210.0 mg; 0.6 mmol) in tetrahydrofuran (500 μL). Allow the resulting mixture to warm to room temperature and stir for 2 hours. Add 1M HCl, dilute with ether and pass through an SCX acidic ion exchange column. Flush the column with methanol then elute desired material with 2M ammonia in methanol. Concentrate the ammonia containing eluent to give a yellow solid. Purify the yellow solid on a silica gel flash chromatography to obtain the title compound (59.0 mg, 0.1 mmol): mass spectrum (m/z): 478 (M+1).

Workup

  1. temperatureWarm the resulting solution to 0° C.
  2. temperatureto warm to room temperature
  3. stirringstir for 2 hours
  4. customFlush the column with methanol
  5. washthen elute desired material with 2M ammonia in methanol
  6. concentrationConcentrate the ammonia containing eluent
  7. customto give a yellow solid
  8. customPurify the yellow solid on a silica gel flash chromatography

Sources & evidence

ORD record
ord-6b156cc241b14e6bb61f2247ecf0f7c3
Source dataset
uspto-grants-2013_07
Patent number
US08476300B2

Reaction notes

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