tert-butyl 2-(3-(3-cyanophenethoxy)-N-cyclohexylpropanamido)ethyl(2-(5-hydroxy-3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazin-8-yl)ethyl)carbamate → tert-Butyl 2-(N-cyclohexyl-3-(3-formylphenethoxy)propanamido)ethyl(2-(5-hydroxy-3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazin-8-yl)ethyl)carbamate

HRID 446475Notes

Reaction equation

HRID 446475 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]([CH:44]=[CH:45][CH:46]=1)[CH2:6][CH2:7][O:8][CH2:9][CH2:10][C:11]([N:13]([CH2:20][CH2:21][N:22]([CH2:30][CH2:31][C:32]1[C:37]2[O:38][CH2:39][C:40](=[O:42])[NH:41][C:36]=2[C:35]([OH:43])=[CH:34][CH:33]=1)[C:23](=[O:29])[O:24][C:25]([CH3:28])([CH3:27])[CH3:26])[CH:14]1[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15]1)=[O:12])#N.O.[PH2]([O-])=[O:49].[Na+]>N1C=CC=CC=1.C(O)(=O)C.O.[Ni]>[CH:14]1([N:13]([CH2:20][CH2:21][N:22]([CH2:30][CH2:31][C:32]2[C:37]3[O:38][CH2:39][C:40](=[O:42])[NH:41][C:36]=3[C:35]([OH:43])=[CH:34][CH:33]=2)[C:23](=[O:29])[O:24][C:25]([CH3:26])([CH3:28])[CH3:27])[C:11](=[O:12])[CH2:10][CH2:9][O:8][CH2:7][CH2:6][C:5]2[CH:44]=[CH:45][CH:46]=[C:3]([CH:1]=[O:49])[CH:4]=2)[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15]1

Participants

7

Reactant 2

HCID 58168493tert-butyl 2-(3-(3-cyanophenethoxy)-N-cyclohexylpropanamido)ethyl(2-(5-hydroxy-3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazin-8-yl)ethyl)carbamateHCID 178418950HCID 178418950, compound

Product 1

HCID 58168538tert-Butyl 2-(N-cyclohexyl-3-(3-formylphenethoxy)propanamido)ethyl(2-(5-hydroxy-3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazin-8-yl)ethyl)carbamate

Reagents, catalysts & solvents 4

HCID 935NickelCatalystHCID 176Acetic AcidSolventHCID 962WaterSolventHCID 1049PyridineSolvent

Conditions

Temperature
45 °C

Procedure

To a stirred solution of tert-butyl 2-(3-(3-cyanophenethoxy)-N-cyclohexylpropanamido)ethyl(2-(5-hydroxy-3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazin-8-yl)ethyl)carbamate [Examples 81-175, step e] (7.3 g) in pyridine (115 mL), acetic acid (58 mL) and water (58 mL), pre-cooled in ice-water under nitrogen, was added sodium hypophosphite monohydrate (14.6 g) followed by Raney® nickel (50% in water, 3.0 g). The reaction mixture was stirred at 45° C. for 8 hours, then allowed to cool and stand over a weekend. Celite was added and the suspension was filtered through a pad of Celite, washing the residue well with acetic acid and ethyl acetate. The filtrate was washed three times with water, once with brine, then dried (MgSO4), filtered and concentrated in-vacuo. The residue was azeotroped twice with toluene to afford the subtitled compound as a pale yellow foam. Yield 6.6 g.

Workup

  1. temperatureto cool
  2. waitstand over a weekend
  3. additionCelite was added
  4. filtrationthe suspension was filtered through a pad of Celite
  5. washwashing the residue well with acetic acid and ethyl acetate
  6. washThe filtrate was washed three times with water
  7. dry with materialonce with brine, then dried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated in-vacuo
  10. customThe residue was azeotroped twice with toluene

Sources & evidence

ORD record
ord-3a93ff92079345ea809edec54a4009f7
Source dataset
uspto-grants-2013_07
Patent number
US08476265B2

Reaction notes

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