Sodium Hydroxide → 4-[3-{[[((3R,4S)-1-(tert-Butoxycarbonyl)-4-{4-[2-(2,6-dichloro-4-methylphenoxy)ethoxy]phenyl}piperidin-3-yl)carbonyl](cyclopropyl)amino]methyl}-5-(3-methoxypropyl)phenoxy]-2,2-dimethylbutanoic acid

HRID 1798483Notes

Reaction equation

HRID 1798483 reaction equation
[CH:1]1([N:4]([CH2:39][C:40]2[CH:45]=[C:44]([CH2:46][CH2:47][CH2:48][O:49][CH3:50])[CH:43]=[C:42]([O:51][CH2:52][CH2:53][C:54]([CH3:60])([CH3:59])[C:55]([O:57]C)=[O:56])[CH:41]=2)[C:5]([C@@H:7]2[C@@H:12]([C:13]3[CH:18]=[CH:17][C:16]([O:19][CH2:20][CH2:21][O:22][C:23]4[C:28]([Cl:29])=[CH:27][C:26]([CH3:30])=[CH:25][C:24]=4[Cl:31])=[CH:15][CH:14]=3)[CH2:11][CH2:10][N:9]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH2:8]2)=[O:6])[CH2:3][CH2:2]1.[OH-].[Na+]>C(O)C>[C:35]([O:34][C:32]([N:9]1[CH2:10][CH2:11][C@H:12]([C:13]2[CH:18]=[CH:17][C:16]([O:19][CH2:20][CH2:21][O:22][C:23]3[C:24]([Cl:31])=[CH:25][C:26]([CH3:30])=[CH:27][C:28]=3[Cl:29])=[CH:15][CH:14]=2)[C@@H:7]([C:5]([N:4]([CH2:39][C:40]2[CH:41]=[C:42]([CH:43]=[C:44]([CH2:46][CH2:47][CH2:48][O:49][CH3:50])[CH:45]=2)[O:51][CH2:52][CH2:53][C:54]([CH3:59])([CH3:60])[C:55]([OH:57])=[O:56])[CH:1]2[CH2:3][CH2:2]2)=[O:6])[CH2:8]1)=[O:33])([CH3:38])([CH3:37])[CH3:36]

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 86641751HCID 86641751, compound

Product 1

HCID 684885934-[3-{[[((3R,4S)-1-(tert-Butoxycarbonyl)-4-{4-[2-(2,6-dichloro-4-methylphenoxy)ethoxy]phenyl}piperidin-3-yl)carbonyl](cyclopropyl)amino]methyl}-5-(3-methoxypropyl)phenoxy]-2,2-dimethylbutanoic acid

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of tert-Butyl (3R,4S)-3-({cyclopropyl[3-(4-methoxy-3,3-dimethyl-4-oxobutoxy)-5-(3-methoxypropyl)-benzyl]amino}carbonyl)-4-{4-[2-(2,6-dichloro-4-methylphenoxy)ethoxy]phenyl}-piperidine-1-carboxylate (1 eq.) from Example 21/Step 2 in ethanol was added 1 N aqueous NaOH (3 eq.). The reaction was heated to 100° C. for 10 min in a microwave reactor (Biotage). After cooling to rt, the reaction was concentrated in vacuo to removed the ethanol solvent. The resulting solution was acidified with 1 N HCl and extracted with ethyl acetate. The combined organic extracted were dried over anhydrous Na2SO4 and concentrated in vacuo. The crude product was used in the next step without further purification.

Workup

  1. temperatureAfter cooling to rt
  2. concentrationthe reaction was concentrated in vacuo
  3. customto removed the ethanol solvent
  4. extractionextracted with ethyl acetate
  5. extractionThe combined organic extracted
  6. dry with materialwere dried over anhydrous Na2SO4
  7. concentrationconcentrated in vacuo
  8. customThe crude product was used in the next step without further purification

Sources & evidence

ORD record
ord-eaf63d490ec74afd8e81da750f3f6ab1
Source dataset
uspto-grants-2013_01
Patent number
US08343968B2

Reaction notes

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