Triphenylphosphine → HCID 118307721, compound

HRID 718442Notes

Reaction equation

HRID 718442 reaction equation
[C:1]([O:5][C@@H:6]([C:12]1[C:13]([CH3:34])=[N:14][C:15]([CH3:33])=[C:16]([C:26]2[CH:31]=[CH:30][C:29](O)=[CH:28][CH:27]=2)[C:17]=1[N:18]1[CH2:23][CH2:22][C:21]([CH3:25])([CH3:24])[CH2:20][CH2:19]1)[C:7]([O:9]CC)=[O:8])([CH3:4])([CH3:3])[CH3:2].[C:35]1([CH3:44])[CH:40]=[CH:39][C:38]([CH2:41][CH2:42][OH:43])=[CH:37][CH:36]=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CCOC(/N=N/C(OCC)=O)=O.[OH-].[Na+]>C1COCC1.CO>[C:1]([O:5][C@@H:6]([C:12]1[C:13]([CH3:34])=[N:14][C:15]([CH3:33])=[C:16]([C:26]2[CH:27]=[CH:28][C:29]([O:43][CH2:42][CH2:41][C:38]3[CH:39]=[CH:40][C:35]([CH3:44])=[CH:36][CH:37]=3)=[CH:30][CH:31]=2)[C:17]=1[N:18]1[CH2:19][CH2:20][C:21]([CH3:25])([CH3:24])[CH2:22][CH2:23]1)[C:7]([OH:9])=[O:8])([CH3:4])([CH3:2])[CH3:3]

Participants

8

Reactant 5

HCID 11776TriphenylphosphineHCID 14798Sodium HydroxideHCID 952944-Methylphenethyl alcoholHCID 5462977Diethyl azodicarboxylateHCID 118314205(S)-ethyl 2-(tert-butoxy)-2-(4-(4,4-dimethylpiperidin-1-yl)-5-(4-hydroxyphenyl)-2,6-dimethylpyridin-3-yl)acetate

Product 1

HCID 118307721HCID 118307721, compoundYield 30.6%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of (S)-ethyl 2-(tert-butoxy)-2-(4-(4,4-dimethylpiperidin-1-yl)-5-(4-hydroxyphenyl)-2,6-dimethylpyridin-3-yl)acetate (20 mg, 0.043 mmol), 2-(p-tolyl)ethanol (29.1 mg, 0.213 mmol) and Ph3P-resin (55.8 mg, 0.213 mmol) in THF (2 mL) was added DEAD (0.014 mL, 0.085 mmol) at rt. After 18 h, mixture was filtered to remove polymer, concentrated and treated with 1N NaOH (0.854 mL, 0.854 mmol) in MeOH (1 mL) at 75° C. for 16 h. Mixture was then cooled and purified by prep-HPLC to afford (S)-2-(tert-butoxy)-2-(4-(4,4-dimethylpiperidin-1-yl)-2,6-dimethyl-5-(4-(4-methylphenethoxy)phenyl)pyridin-3-yl)acetic acid (7.3 mg, 0.013 mmol, 30.6% yield). 1H NMR (500 MHz, DMSO-d6) δ 7.17 (d, J=7.7 Hz, 3H), 7.09 (d, J=8.1 Hz, 2H), 7.02-6.93 (m, 3H), 5.80 (br. s., 1H), 4.25-4.13 (m, 2H), 2.96 (t, J=6.2 Hz, 2H), 2.41 (s, 3H), 2.24 (s, 3H), 2.03 (s, 3H), 1.21 (br. s., 2H), 1.09 (s, 9H), 0.77 (s., 3H), 0.62 (s., 3H). 6H of piperidine were not resolved. LCMS (M+H)=559.15.

Workup

  1. filtrationmixture was filtered
  2. customto remove polymer
  3. concentrationconcentrated
  4. temperatureMixture was then cooled
  5. custompurified by prep-HPLC

Sources & evidence

ORD record
ord-96ef994ae2224bbcb428bae45c3b6ce3
Source dataset
uspto-grants-2015_11
Patent number
US09193720B2

Reaction notes

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