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

HRID 1798472Notes

Reaction equation

HRID 1798472 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][C:53]3([CH2:56][C:57]([O:59]C)=[O:58])[CH2:55][CH2:54]3)[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:28]([Cl:29])=[CH:27][C:26]([CH3:30])=[CH:25][C:24]=3[Cl:31])=[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][C:53]2([CH2:56][C:57]([OH:59])=[O:58])[CH2:54][CH2:55]2)[CH:1]2[CH2:2][CH2:3]2)=[O:6])[CH2:8]1)=[O:33])([CH3:36])([CH3:37])[CH3:38]

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 86641743tert-butyl (3R,4S)-3-({cyclopropyl[3-{[1-(2-methoxy-2-oxoethyl)cyclopropyl]methoxy}-5-(3-methoxypropyl)benzyl]amino}carbonyl)-4-{4-[2-(2,6-dichloro-4-methylphenoxy)ethoxy]phenyl}piperidine-1-carboxylate

Product 1

HCID 68492241(1-{[3-{[[((3R,4S)-1-(tert-Butoxycarbonyl)-4-{4-[2-(2,6-dichloro-4-methyl-phenoxy)ethoxy]phenyl}piperidin-3-yl)carbonyl](cyclopropyl)amino]methyl}-5-(3-methoxypropyl)phenoxy]methyl}cyclopropyl)acetic Acid

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of tert-butyl (3R,4S)-3-({cyclopropyl[3-{[1-(2-methoxy-2-oxoethyl)cyclopropyl]methoxy}-5-(3-methoxypropyl)benzyl]amino}carbonyl)-4-{4-[2-(2,6-dichloro-4-methylphenoxy)ethoxy]phenyl}piperidine-1-carboxylate (1 eq.) from Example 11/Step Step 1 in ethanol (0.1 M) was added 1 M aqueous NaOH (3 eq.). The reaction was heated at 100° C. in a microwave (Biotage) for 5 min. The reaction was cooled to rt and concentrated in vacuo. The residue was suspended in 1 N aqueous HCl and EtOAc. The aqueous layer was extracted several times with EtOAc. The combined organic extracts were washed with brine, dried over MgSO4, and concentrated in vacuo to afford the title compound as a foam.

Workup

  1. temperatureThe reaction was cooled to rt
  2. concentrationconcentrated in vacuo
  3. extractionThe aqueous layer was extracted several times with EtOAc
  4. washThe combined organic extracts were washed with brine
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-1820096b17454c208ed9612a3101fbbc
Source dataset
uspto-grants-2013_01
Patent number
US08343968B2

Reaction notes

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