2-(2-Hydroxyethyl)pyridine → tert-Butyl (3-{cyclopropyl[3-(3-methoxypropyl)-5-(2-pyridin-2-ylethoxy)benzyl]amino}-2-{4-[2-(2,6-dichloro-4-methylphenoxy)ethoxy]benzyl}-3-oxopropyl)carbamate

HRID 561877Notes

Reaction equation

HRID 561877 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.[N:53]1[CH:58]=[CH:57][CH:56]=[CH:55][C:54]=1[CH2:59][CH2:60]O.N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O.C(P(CCCC)CCCC)CCC>C1(C)C=CC=CC=1.CCOCC>[CH:4]1([N:7]([CH2:40][C:41]2[CH:42]=[C:43]([O:52][CH2:60][CH2:59][C:54]3[CH:55]=[CH:56][CH:57]=[CH:58][N:53]=3)[CH:44]=[C:45]([CH2:47][CH2:48][CH2:49][O:50][CH3:51])[CH:46]=2)[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:18])[O:13][C:14]([CH3:16])([CH3:17])[CH3:15])[CH2:5][CH2:6]1

Participants

7

Reactant 4

HCID 76752-(2-Hydroxyethyl)pyridineHCID 13831TributylphosphineHCID 730421,1'-(Azodicarbonyl)dipiperidineHCID 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 86635939tert-Butyl (3-{cyclopropyl[3-(3-methoxypropyl)-5-(2-pyridin-2-ylethoxy)benzyl]amino}-2-{4-[2-(2,6-dichloro-4-methylphenoxy)ethoxy]benzyl}-3-oxopropyl)carbamate

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 3283Diethyl EtherSolvent

Conditions

Temperature
100 °C

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 toluene (0.1 M) was added 2-pyridin-2-ylethanol (1.2 eq.) and 1,1′-(azodicarbonyl)-dipiperidine (1.2 eq.). The resulting orange solution was deoxygenated before tributylphosphine (1.2 eq.) was added. The now yellow-orange solution was heated at 100° C. for 14 h. The reaction mixture was cooled to RT, diluted with ether, and washed with 1 N aq. NaOH. The aqueous wash was back extracted with ether and the combined organic extracts were dried over MgSO4. Filtration and concentration of the filtrate in vacuo afforded a red oil. Purification of the crude product thus obtained by way of flash chromatography (SiO2, 4:1 (v/v) Hex:EtOAc→EtOAc) afforded the title compound as a pale yellow oil.

Workup

  1. additionwas added
  2. temperatureThe reaction mixture was cooled to RT
  3. washwashed with 1 N aq. NaOH
  4. washThe aqueous wash
  5. extractionwas back extracted with ether
  6. dry with materialthe combined organic extracts were dried over MgSO4
  7. filtrationFiltration and concentration of the filtrate in vacuo
  8. customafforded a red oil
  9. customPurification of the crude product
  10. customthus obtained by way of flash chromatography (SiO2, 4:1 (v/v) Hex:EtOAc→EtOAc)

Sources & evidence

ORD record
ord-7ed98a70343f42148656a22fe93acaa6
Source dataset
uspto-grants-2011_11
Patent number
US08063105B2

Reaction notes

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