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

HRID 1176601Notes

Reaction equation

HRID 1176601 reaction equation
[NH2:1][CH2:2][CH2:3][O:4][C:5]1[CH:10]=[CH:9][C:8]([CH:11]2[CH2:16][CH2:15][N:14]([C:17]([O:19][CH2:20][C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)=[O:18])[CH2:13][CH:12]2[O:27][CH2:28][C:29]2[CH:30]=[CH:31][C:32]3[O:37][CH2:36][CH2:35][N:34]([CH2:38][CH2:39][CH2:40][O:41][CH3:42])[C:33]=3[CH:43]=2)=[CH:7][CH:6]=1.[F:44][C:45]1[CH:50]=[CH:49][C:48]([CH2:51][CH:52]=O)=[CH:47][CH:46]=1.C([O-])(=O)C.[Na+].C([BH3-])#N.[Na+].C(=O)([O-])O.[Na+]>O1CCCC1.CO>[F:44][C:45]1[CH:50]=[CH:49][C:48]([CH2:51][CH2:52][NH:1][CH2:2][CH2:3][O:4][C:5]2[CH:6]=[CH:7][C:8]([CH:11]3[CH2:16][CH2:15][N:14]([C:17]([O:19][CH2:20][C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=4)=[O:18])[CH2:13][CH:12]3[O:27][CH2:28][C:29]3[CH:30]=[CH:31][C:32]4[O:37][CH2:36][CH2:35][N:34]([CH2:38][CH2:39][CH2:40][O:41][CH3:42])[C:33]=4[CH:43]=3)=[CH:9][CH:10]=2)=[CH:47][CH:46]=1

Participants

8

Reactant 5

HCID 516892Sodium BicarbonateHCID 517045Sodium AcetateHCID 5003444Sodium cyanoborohydrideHCID 111263222-(4-Fluorophenyl)acetaldehydeHCID 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 68500702Benzyl 4-(4-{2-[2-(4-fluorophenyl)ethylamino]ethoxy}phenyl)-3-[4-(3-methoxypropyl)-3,4-dihydro-2H-benzo[1,4]oxazin-6-ylmethoxy]piperidine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent2×HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
20 °C

Procedure

0.361 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) is dissolved under argon in tetrahydrofuran. 2 g of 4 Å molecular sieve are added, followed by a solution of (4-fluorophenyl)acetaldehyde in 1 ml of tetrahydrofuran. The reaction mixture is stirred at 20° C. for 2 hours. 3 ml of methanol and 0.078 g of sodium acetate are added to the mixture. A solution of 0.055 g of sodium cyanoborohydride in 3 ml of methanol is added dropwise at 0° C. and the mixture is subsequently stirred at 0° C. over 1 hour. 10 ml of saturated aqueous sodium hydrogencarbonate solution are added and the mixture is subsequently filtered through Hyflo. The filtrate is extracted with ethyl acetate (2×20 ml)—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=0.20 (200:5:1 dichloromethane-methanol-25% conc. ammonia); Rt=4.74.

Workup

  1. addition2 g of 4 Å molecular sieve are added
  2. stirringthe mixture is subsequently stirred at 0° C. over 1 hour
  3. filtrationthe mixture is subsequently filtered through Hyflo
  4. extractionThe filtrate is extracted with ethyl acetate (2×20 ml)—the combined organic phases
  5. washare washed with 20 ml of brine
  6. dry with materialdried over sodium sulphate
  7. concentrationconcentrated by evaporation

Sources & evidence

ORD record
ord-20b932198c1c478aa86fb0927391393c
Source dataset
uspto-grants-2010_11
Patent number
US07842688B2

Reaction notes

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