Sodium Hydroxide → 3-{[(3-[(tert-Butoxycarbonyl)amino]-2-{4-[2-(2,6-dichloro-4-methylphenoxy)ethoxy]benzyl}propanoyl)(cyclopropyl)amino]methyl]-5-(3-methoxypropyl)phenyl (3-amino-2,2-dimethyl-3-oxopropyl)carbamate

HRID 561889Notes

Reaction equation

HRID 561889 reaction equation
C1([C:4]2([N:7]([CH2:40][C:41]3[CH:46]=[C:45]([CH2:47][CH2:48][CH2:49][O:50][CH3:51])[CH:44]=[C:43]([OH:52])[CH:42]=3)[C:8](=[O:39])[CH:9]([CH2:19][C:20]3[CH:25]=[CH:24][C:23]([O:26][CH2:27][CH2:28][O:29][C:30]4[C:35]([Cl:36])=[CH:34][C:33]([CH3:37])=[CH:32][C:31]=4[Cl:38])=[CH:22][CH:21]=3)[CH2:10][NH:11][C:12](=[O:18])[O:13][C:14]([CH3:17])([CH3:16])[CH3:15])[CH2:6][CH2:5]2)CC1.Cl[C:54](Cl)([O:56]C(=O)OC(Cl)(Cl)Cl)Cl.[OH-].[Na+].[NH2:67][CH2:68][C:69]([CH3:74])([CH3:73])[C:70]([NH2:72])=[O:71]>ClCCl>[NH2:72][C:70](=[O:71])[C:69]([CH3:74])([CH3:73])[CH2:68][NH:67][C:54](=[O:56])[O:52][C:43]1[CH:44]=[C:45]([CH2:47][CH2:48][CH2:49][O:50][CH3:51])[CH:46]=[C:41]([CH2:40][N:7]([C:8](=[O:39])[CH:9]([CH2:19][C:20]2[CH:25]=[CH:24][C:23]([O:26][CH2:27][CH2:28][O:29][C:30]3[C:35]([Cl:36])=[CH:34][C:33]([CH3:37])=[CH:32][C:31]=3[Cl:38])=[CH:22][CH:21]=2)[CH2:10][NH:11][C:12]([O:13][C:14]([CH3:17])([CH3:15])[CH3:16])=[O:18])[CH:4]2[CH2:5][CH2:6]2)[CH:42]=1

Participants

6

Reactant 4

HCID 14798Sodium HydroxideHCID 94429TriphosgeneHCID 111593153-Amino-2,2-dimethylpropanamideHCID 86635933tert-Butyl (3-{cyclopropyl[3-hydroxy-5-(3-methoxypropyl)benzyl](cyclopropyl)amino}-2-{4-[2-(2,6-dichloro-4-methylphenoxy)ethoxy]benzyl}-3-oxopropyl)carbamate

Product 1

HCID 866359473-{[(3-[(tert-Butoxycarbonyl)amino]-2-{4-[2-(2,6-dichloro-4-methylphenoxy)ethoxy]benzyl}propanoyl)(cyclopropyl)amino]methyl]-5-(3-methoxypropyl)phenyl (3-amino-2,2-dimethyl-3-oxopropyl)carbamate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of tert-butyl (3-{cyclopropyl[3-hydroxy-5-(3-methoxypropyl)benzyl] (cyclopropyl)amino}-2-{4-[2-(2,6-dichloro-4-methylphenoxy)ethoxy]benzyl}-3-oxopropyl)carbamate from Example 70, Step 2 (1 eq.) in dichloromethane (0.13 M) was added triphosgene (0.3 eq.) and then sodium hydroxide (1 M aq. solution, 3 eq.). The resulting mixture was stirred at RT for 2 h. The reaction was quenched with brine. The organic phase was separated and then added 3-amino-2,2-dimethylpropanamide (4 eq.). The resulting suspension was allowed to stir at RT for 16 h. The reaction was quenched with water and then extracted with EtOAc. The combined organic extracts were washed with brine, dried over MgSO4, filtered, and the filtrate concentrated in vacuo. The crude product thus obtained was purified further by way of column chromatography (SiO2, 1:1 (v/v) Hex:EtOAc→EtOAc) to afford the title compound as a colorless oil.

Workup

  1. customThe reaction was quenched with brine
  2. customThe organic phase was separated
  3. stirringto stir at RT for 16 h
  4. customThe reaction was quenched with water
  5. extractionextracted with EtOAc
  6. washThe combined organic extracts were washed with brine
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationthe filtrate concentrated in vacuo
  10. customThe crude product thus obtained
  11. customwas purified further by way of column chromatography (SiO2, 1:1 (v/v) Hex:EtOAc→EtOAc)

Sources & evidence

ORD record
ord-56768205444a497798ced1216e755f7a
Source dataset
uspto-grants-2011_11
Patent number
US08063105B2

Reaction notes

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