Triphenylphosphine → tert-butyl(2S)-2-(3-{2-[({(3RS,4RS)-3-(2,4-dichlorophenyl)-2-[(1SR,2SR)-2-hydroxycyclohexyl]-1-oxo-1,2,3,4-tetrahydroisoquinolin-4-yl}carbonyl)amino]ethyl}phenoxy)propanate

HRID 1747102Notes

Reaction equation

HRID 1747102 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[CH:9]1[CH:18]([C:19]([NH:21][CH2:22][CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[C:26]([OH:30])[CH:25]=2)=[O:20])[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[C:11](=[O:31])[N:10]1[CH:32]1[CH2:37][CH2:36][CH2:35][CH2:34][CH:33]1[OH:38].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.O[C@H:59]([CH3:67])[C:60]([O:62][C:63]([CH3:66])([CH3:65])[CH3:64])=[O:61].N(C(OCC)=O)=NC(OCC)=O>C(OCC)(=O)C.C1COCC1>[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[CH:9]1[CH:18]([C:19]([NH:21][CH2:22][CH2:23][C:24]2[CH:25]=[C:26]([CH:27]=[CH:28][CH:29]=2)[O:30][C@@H:59]([CH3:67])[C:60]([O:62][C:63]([CH3:66])([CH3:65])[CH3:64])=[O:61])=[O:20])[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[C:11](=[O:31])[N:10]1[CH:32]1[CH2:37][CH2:36][CH2:35][CH2:34][CH:33]1[OH:38]

Participants

7

Reactant 4

HCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 10953655tert-butyl (2R)-2-hydroxypropanoateHCID 68449574(3RS,4RS)-3-(2,4-dichlorophenyl)-2-[(1SR,2SR)-2-hydroxycyclohexyl]-N-[2-(3-hydroxyphenyl)ethyl]-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxamide

Product 1

HCID 86711699tert-butyl(2S)-2-(3-{2-[({(3RS,4RS)-3-(2,4-dichlorophenyl)-2-[(1SR,2SR)-2-hydroxycyclohexyl]-1-oxo-1,2,3,4-tetrahydroisoquinolin-4-yl}carbonyl)amino]ethyl}phenoxy)propanateYield 121%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a mixture of 980 mg of (3RS,4RS)-3-(2,4-dichlorophenyl)-2-[(1SR,2SR)-2-hydroxycyclohexyl]-N-[2-(3-hydroxyphenyl)ethyl]-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxamide, 1160 mg of triphenylphosphine, 1080 mg of tert-butyl(2R)-2-hydroxypropanate, and 30 mL of THF was added 770 mg of diethyl azodicarboxylate at room temperature, followed by stirring for 12 hours. The reaction solution was diluted with ethyl acetate and washed with a saturated aqueous sodium hydrogen carbonate solution. The organic layer was dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (eluent:chloroform-methanol) to obtain 1460 mg of tert-butyl(2S)-2-(3-{2-[({(3RS,4RS)-3-(2,4-dichlorophenyl)-2-[(1SR,2SR)-2-hydroxycyclohexyl]-1-oxo-1,2,3,4-tetrahydroisoquinolin-4-yl}carbonyl)amino]ethyl}phenoxy)propanate as a yellow solid.

Workup

  1. washwashed with a saturated aqueous sodium hydrogen carbonate solution
  2. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  3. concentrationconcentrated under reduced pressure
  4. customThe obtained residue was purified by silica gel column chromatography (eluent:chloroform-methanol)

Sources & evidence

ORD record
ord-e704791151104266a20c56ff71209b3e
Source dataset
uspto-grants-2015_10
Patent number
US09150541B2

Reaction notes

Loading…