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

HRID 1176525Notes

Reaction equation

HRID 1176525 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.[CH:44]1([CH:50]=O)[CH2:49][CH2:48][CH2:47][CH2:46][CH2:45]1.[BH4-].[Na+].[OH-].[Na+]>CO>[CH:44]1([CH2:50][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)[CH2:49][CH2:48][CH2:47][CH2:46][CH2:45]1

Participants

6

Reactant 4

HCID 14798Sodium HydroxideHCID 16275CyclohexanecarboxaldehydeHCID 4311764Sodium borohydrideHCID 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 68500847Benzyl 4-{4-[2-(cyclohexylmethylamino)ethoxy]phenyl}-3-[4-(3-methoxypropyl)-3,4-dihydro-2H-benzo[1,4]oxazin-6-ylmethoxy]piperidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of 0.346 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 184b) and 0.068 ml of cyclohexanecarbaldehyde in 2 ml of methanol is stirred at room temperature over 3.5 hours, admixed in portions with 0.037 g of sodium borohydride and subsequently stirred for a further 2 hours. The reaction mixture is admixed with 2 ml of 1N NaOH, stirred for 30 minutes and then partitioned between ethyl acetate and water. The organic phase is washed with brine, dried over sodium sulphate and concentrated by evaporation. The title compound is obtained as a yellow oil from the residue by means of flash chromatography (SiO2 60F). Rf=0.48 (200:20:1 dichloromethane-methanol-25% conc. ammonia); Rt=4.97.

Workup

  1. stirringstirred for 30 minutes
  2. custompartitioned between ethyl acetate and water
  3. washThe organic phase is washed with brine
  4. dry with materialdried over sodium sulphate
  5. concentrationconcentrated by evaporation

Sources & evidence

ORD record
ord-98d6f193e8e34aa3a820fa7d396a9524
Source dataset
uspto-grants-2010_11
Patent number
US07842688B2

Reaction notes

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