tert-Butyl acrylate → HCID 86613591, compound

HRID 1365531Notes

Reaction equation

HRID 1365531 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C@@:8]([NH:30][C:31]([NH:33][C@H:34]2[CH2:38][CH2:37][CH2:36][C@H:35]2[OH:39])=[O:32])([C:16]2[CH:21]=[C:20]([O:22][C:23]([F:28])([F:27])[CH:24]([F:26])[F:25])[CH:19]=[C:18]([F:29])[CH:17]=2)[CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[N:6][CH:7]=1.[H-].[Na+].[C:42]([O:46][C:47]([CH3:50])([CH3:49])[CH3:48])(=[O:45])[CH:43]=[CH2:44]>C1COCC1>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C@@:8]([NH:30][C:31](=[O:32])[NH:33][C@H:34]2[CH2:38][CH2:37][CH2:36][C@H:35]2[O:39][CH2:44][CH2:43][C:42]([OH:46])=[O:45])([C:16]2[CH:21]=[C:20]([O:22][C:23]([F:27])([F:28])[CH:24]([F:26])[F:25])[CH:19]=[C:18]([F:29])[CH:17]=2)[CH2:9][C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=2)=[N:6][CH:7]=1.[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C@@:8]([NH:30][C:31](=[O:32])[NH:33][C@H:34]2[CH2:38][CH2:37][CH2:36][C@H:35]2[O:39][CH2:44][CH2:43][C:42]([O:46][C:47]([CH3:50])([CH3:49])[CH3:48])=[O:45])([C:16]2[CH:21]=[C:20]([O:22][C:23]([F:27])([F:28])[CH:24]([F:26])[F:25])[CH:19]=[C:18]([F:29])[CH:17]=2)[CH2:9][C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=2)=[N:6][CH:7]=1

Participants

6

Reactant 3

HCID 15458tert-Butyl acrylateHCID 24758Sodium hydrideHCID 86612969HCID 86612969, compound

Product 2

HCID 86613591HCID 86613591, compoundHCID 86613592HCID 86613592, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 1-((S)-1-(5-chloropyridin-2-yl)-1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-2-phenylethyl)-3-((1S,2R)-2-hydroxycyclopentyl)urea (16 mg, 0.028 mmol) in THF (1 mL) was added NaH (11 mg, 60% in mineral oil, 0.28 mmol). t-Butyl acrylate (18 mg, 0.14 mmol) was added after 1 min and the reaction mixture stirred at ambient temperature for 16 h. The reaction mixture was concentrated in vacuo and purified by preparative HPLC Shimadzu-Phenomenex Luna C18 column, 21.2×100 mm eluting with 10-100% CH3CN (90% in H2O, 0.1% TFA) gradient over 15 min with flow rate 20 mL/min and UV detection at 220 nm to give 3-((1R,2S)-2-(3-((S)-1-(5-chloropyridin-2-yl)-1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-2-phenylethyl)ureido)cyclopentyloxy)propanoic acid at the retention time of 8.74 min (1.2 mg, 6% yield) and tert-butyl 3-((1R,2S)-2-(3-((S)-1-(5-chloropyridin-2-yl)-1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-2-phenylethyl)ureido)cyclopentyloxy)propanoate at a retention time of 11.32 min (2.5 mg, 14% yield).

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. custompurified by preparative HPLC Shimadzu-Phenomenex Luna C18 column, 21.2×100 mm
  3. washeluting with 10-100% CH3CN (90% in H2O, 0.1% TFA) gradient over 15 min with flow rate 20 mL/min and UV detection at 220 nm

Sources & evidence

ORD record
ord-d9fe71c718394103b616c7a5dc4b57a8
Source dataset
uspto-grants-2011_02
Patent number
US07888376B2

Reaction notes

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