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 → Benzyl 4-(4-{2-[2-(2-fluorophenyl)ethylamino]ethoxy}phenyl)-3-[4-(3-methoxypropyl)-3,4-dihydro-2H-benzo[1,4]oxazin-6-ylmethoxy]piperidine-1-carboxylate

HRID 1176604Notes

Reaction equation

HRID 1176604 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:8][C:9]([NH:11][CH2:12][CH2:13][O:14][C:15]1[CH:20]=[CH:19][C:18]([CH:21]2[CH2:26][CH2:25][N:24]([C:27]([O:29][CH2:30][C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=3)=[O:28])[CH2:23][CH:22]2[O:37][CH2:38][C:39]2[CH:40]=[CH:41][C:42]3[O:47][CH2:46][CH2:45][N:44]([CH2:48][CH2:49][CH2:50][O:51][CH3:52])[C:43]=3[CH:53]=2)=[CH:17][CH:16]=1)=O.B#B.O1CCCC1>O1CCCC1>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:8][CH2:9][NH:11][CH2:12][CH2:13][O:14][C:15]1[CH:16]=[CH:17][C:18]([CH:21]2[CH2:26][CH2:25][N:24]([C:27]([O:29][CH2:30][C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=3)=[O:28])[CH2:23][CH:22]2[O:37][CH2:38][C:39]2[CH:40]=[CH:41][C:42]3[O:47][CH2:46][CH2:45][N:44]([CH2:48][CH2:49][CH2:50][O:51][CH3:52])[C:43]=3[CH:53]=2)=[CH:19][CH:20]=1

Participants

4

Reactant 2

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-carboxylateHCID 131714434Diborane tetrahydrofuran

Product 1

HCID 68502751Benzyl 4-(4-{2-[2-(2-fluorophenyl)ethylamino]ethoxy}phenyl)-3-[4-(3-methoxypropyl)-3,4-dihydro-2H-benzo[1,4]oxazin-6-ylmethoxy]piperidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 0.455 g of 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 in 5 ml of tetrahydrofuran is admixed at 0° C. with 1.84 ml of diborane-tetrahydrofuran complex (1M solution in tetrahydrofuran). The reaction solution is subsequently heated to reflux over 3 hours. The reaction solution is cooled to room temperature, quenched with 2 ml of methanol and finally admixed with 2 ml of 2M HCl. The mixture is stirred at room temperature over 30 minutes, neutralized with 20 ml of saturated aqueous sodium hydrogencarbonate solution and extracted with 3×20 ml of ethyl acetate. The combined organic phases are washed with 20 ml of brine, dried over sodium sulphate and concentrated by evaporation. The title compound is obtained from the residue by means of flash chromatography (SiO2 60F). Rf=0.52 (200:20:1 dichloromethane-methanol-25% conc. ammonia); Rt=4.83.

Workup

  1. temperatureThe reaction solution is subsequently heated
  2. temperatureto reflux over 3 hours
  3. customquenched with 2 ml of methanol
  4. extractionextracted with 3×20 ml of ethyl acetate
  5. washThe combined organic phases are washed with 20 ml of brine
  6. dry with materialdried over sodium sulphate
  7. concentrationconcentrated by evaporation

Sources & evidence

ORD record
ord-765e417d253f436b9bf338b4861280d0
Source dataset
uspto-grants-2010_11
Patent number
US07842688B2

Reaction notes

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