4-Fluorophenyl isocyanate → HCID 59536314, compound

HRID 445330Notes

Reaction equation

HRID 445330 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([CH:9]2[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[CH2:12][CH2:11][NH:10]2)=[CH:5][CH:4]=1.[F:19][C:20]1[CH:25]=[CH:24][C:23]([N:26]=[C:27]=[O:28])=[CH:22][CH:21]=1>C(Cl)Cl>[F:19][C:20]1[CH:25]=[CH:24][C:23]([NH:26][C:27]([N:10]2[CH2:11][CH2:12][C:13]3[C:18](=[CH:17][CH:16]=[CH:15][CH:14]=3)[CH:9]2[C:6]2[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:8][CH:7]=2)=[O:28])=[CH:22][CH:21]=1

Participants

4

Reactant 2

HCID 709554-Fluorophenyl isocyanateHCID 12267903HCID 12267903, compound

Product 1

HCID 59536314HCID 59536314, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a round-bottomed flask containing crude 1-(4-methoxyphenyl)-1,2,3,4-tetrahydroisoquinoline (25 mg, 104 μmol) and CH2Cl2 (10 mL) was added 1-fluoro-4-isocyanatobenzene (0.03 mL, 264 μmol). The solution was stirred at RT. After 1 h, the reaction was concentrated in vacuo and taken up in DMF and purified by reverse-phase preparative HPLC (Shimadzu) on a Phenomenex Gemini™ column (5 micron, C18, 110 Å, Axia, 100×50 mm) eluting at 90 mL/min with an linear gradient of 10% to 100% MeCN (0.1% TFA) in water (0.1% TFA) over 10 min to give crude product, that was lypholized and resubjected to the same purification conditions to give N-(4-fluorophenyl)-1-(4-methoxyphenyl)-3,4-dihydroisoquinoline-2(1H)-carboxamide, as a white solid that contained 0.66 eq of TFA. MS (ESI pos. ion) m/z: 377 (M+1).

Workup

  1. concentrationthe reaction was concentrated in vacuo
  2. custompurified by reverse-phase preparative HPLC (Shimadzu) on a Phenomenex Gemini™ column (5 micron, C18, 110 Å, Axia, 100×50 mm)
  3. washeluting at 90 mL/min with an linear gradient of 10% to 100% MeCN (0.1% TFA) in water (0.1% TFA) over 10 min
  4. customto give crude product, that
  5. customresubjected to the same purification conditions

Sources & evidence

ORD record
ord-74c864b0ad364bd68ccb0b8a843c1f1a
Source dataset
uspto-grants-2013_07
Patent number
US08476297B2

Reaction notes

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