Phosgene → HCID 70120141, compound

HRID 482545Notes

Reaction equation

HRID 482545 reaction equation
[CH:1]1([O:6][C:7]2[CH:8]=[C:9]([C@@H:15]([C:23]3[CH:24]=[C:25]([CH:27]=[CH:28][CH:29]=3)N)[CH2:16][C:17]3[CH:22]=[CH:21][N:20]=[CH:19][CH:18]=3)[CH:10]=[CH:11][C:12]=2[O:13][CH3:14])[CH2:5][CH2:4][CH2:3][CH2:2]1.C([N:32](CC)CC)C.[C:37](Cl)(Cl)=[O:38].[F:41][C:42]1[CH:49]=[CH:48][C:45]([CH2:46][NH2:47])=[CH:44][CH:43]=1>ClCCl>[CH:1]1([O:6][C:7]2[CH:8]=[C:9]([C@@H:15]([C:23]3[CH:24]=[CH:25][C:27]([NH:32][C:37]([NH:47][CH2:46][C:45]4[CH:48]=[CH:49][C:42]([F:41])=[CH:43][CH:44]=4)=[O:38])=[CH:28][CH:29]=3)[CH2:16][C:17]3[CH:22]=[CH:21][N:20]=[CH:19][CH:18]=3)[CH:10]=[CH:11][C:12]=2[O:13][CH3:14])[CH2:2][CH2:3][CH2:4][CH2:5]1

Participants

6

Reactant 4

HCID 6371PhosgeneHCID 8471TriethylamineHCID 673264-FluorobenzylamineHCID 18664801HCID 18664801, compound

Product 1

HCID 70120141HCID 70120141, compoundYield 46%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 3-[1-(R)-(3-cyclopentyloxy-4-methoxyphenyl)-2-(4-pyridyl)ethyl]aniline (508 mg, 1.3 mmol prepared as described in International Patent specification No. WO95/17386) in dichloromethane (15 ml) at 0° C. was added triethylamine (383 μl, 2.1 eq) and then phosgene (725 μl, 20% solution in toluene (1.9M)). After 20 min at this temperature 4-fluorobenzylamine (160 μl, 1.1 eq) was added and the mixture stirred at this temperature for 20 min and then at room temperature overnight. The reaction mixture was concentrated in vacuo and the residue partitioned between ethyl acetate:H2O (100 ml, 1:1, v:v). The aqueous phase was separated and the organic phase washed with water (50 ml), brine (50 ml), dried (MgSO4), filtered and concentrated in vacuo to give a yellow foam. This was subjected to column chromatography (SiO. 2.5% methanoldichloromethane) to afford the title compound as a pale yellow solid (306 mg, 46%). (Found: C, 72.38; H, 6.32; N, 7.64. C33H34N3O4F. 0.4 H2O requires C, 72.48; H, 6.41; N, 7.68%). δH (CDCl3) 1.54 (2H, br), 1.77 (6H, br), 3,22 (2H, d, J 7.1Hz), 3.72 (3H, s), 4.05 (1H, t, J 7.8Hz), 4.26 (2H, br d J 5.4Hz), 4.62 (1H, br), 5.6 (1H, br), 6.62-6.68 (3H, m), 6.84-6.92 (4H, m), 7.01 (1H, d, J 8.0Hz), 7.08-7.16 (3H, m), 7.26 (2H, s), and 8.30 (2H, d J 5.6Hz). m/z (El) 539 (M+) 332, (20), 255 (17), 254 (100), 124 (17), 93 (13), 69 (11), 41 (32).

Workup

  1. customat room temperature
  2. customovernight
  3. concentrationThe reaction mixture was concentrated in vacuo
  4. customthe residue partitioned between ethyl acetate
  5. customThe aqueous phase was separated
  6. washthe organic phase washed with water (50 ml), brine (50 ml)
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customto give a yellow foam

Sources & evidence

ORD record
ord-25b993977534454aafffd3880177e99a
Source dataset
uspto-grants-1998_08
Patent number
US05798373

Reaction notes

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