Benzeneacetic acid, 2-fluoro- → benzyl 4-(4-{2-[2-(2-fluorophenyl)acetylamino]ethoxy}phenyl)-3-[4-(3-methoxypropyl)-3,4-dihydro-2H-benzo[1,4]oxazin-6-ylmethoxy]piperidine-1-carboxylate

HRID 1176605Notes

Reaction equation

HRID 1176605 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:8][C:9]([OH:11])=O.C(N1C=CN=C1)(N1C=CN=C1)=O.[NH2:24][CH2:25][CH2:26][O:27][C:28]1[CH:33]=[CH:32][C:31]([CH:34]2[CH2:39][CH2:38][N:37]([C:40]([O:42][CH2:43][C:44]3[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=3)=[O:41])[CH2:36][CH:35]2[O:50][CH2:51][C:52]2[CH:53]=[CH:54][C:55]3[O:60][CH2:59][CH2:58][N:57]([CH2:61][CH2:62][CH2:63][O:64][CH3:65])[C:56]=3[CH:66]=2)=[CH:30][CH:29]=1>ClCCl>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:8][C:9]([NH:24][CH2:25][CH2:26][O:27][C:28]1[CH:29]=[CH:30][C:31]([CH:34]2[CH2:39][CH2:38][N:37]([C:40]([O:42][CH2:43][C:44]3[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=3)=[O:41])[CH2:36][CH:35]2[O:50][CH2:51][C:52]2[CH:53]=[CH:54][C:55]3[O:60][CH2:59][CH2:58][N:57]([CH2:61][CH2:62][CH2:63][O:64][CH3:65])[C:56]=3[CH:66]=2)=[CH:32][CH:33]=1)=[O:11]

Participants

5

Reactant 3

HCID 67979Benzeneacetic acid, 2-fluoro-HCID 682631,1'-CarbonyldiimidazoleHCID 68501706benzyl 4-[4-(2-aminoethoxy)phenyl]-3-[4-(3-methoxypropyl)-3,4-dihydro-2H-benzo[1,4]oxazin-6-ylmethoxy]piperidine-1-carboxylate

Product 1

HCID 68498024benzyl 4-(4-{2-[2-(2-fluorophenyl)acetylamino]ethoxy}phenyl)-3-[4-(3-methoxypropyl)-3,4-dihydro-2H-benzo[1,4]oxazin-6-ylmethoxy]piperidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Conditions

Temperature
20 °C

Procedure

0.135 g of 2-fluorophenyl acetic acid is dissolved in 5 ml of dichloromethane. 0.127 g of carbonyldiimidazole is added and the reaction solution is stirred at 20° C. over 1 hour. A solution of 0.472 g of benzyl 4-[4-(2-aminoethoxy]phenyl]-3-[4-(3-methoxypropyl)-3,4-dihydro-2H-benzo[1,4]oxazin-6-ylmethoxy]piperidine-1-carboxylate (Example 184) in 4 ml of dichloromethane is added dropwise and the solution is subsequently stirred at 20° C. over 1 hour. The reaction solution is diluted with 10 ml of dichloromethane and subsequently washed with 10 ml each of 1M NaOH and water, dried over sodium sulphate and concentrated by evaporation. The title compound is obtained as a light yellow resin from the residue by means of flash chromatography (SiO2 60F). Rf=0.20 (4:1 EtOAc-heptane); Rt=5.14.

Workup

  1. stirringthe solution is subsequently stirred at 20° C. over 1 hour
  2. washsubsequently washed with 10 ml each of 1M NaOH and water
  3. dry with materialdried over sodium sulphate
  4. concentrationconcentrated by evaporation

Sources & evidence

ORD record
ord-35b1344fa908466b8055ce7701da5abf
Source dataset
uspto-grants-2010_11
Patent number
US07842688B2

Reaction notes

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