Triphenylphosphine → HCID 118307855, compound

HRID 718445Notes

Reaction equation

HRID 718445 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].[CH3:35][O:36][C:37]1[CH:38]=[C:39]([CH2:43][CH2:44][OH:45])[CH:40]=[CH:41][CH:42]=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:45][CH2:44][CH2:43][C:39]3[CH:40]=[CH:41][CH:42]=[C:37]([O:36][CH3:35])[CH:38]=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 787243-Methoxyphenethyl 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 118307855HCID 118307855, compoundYield 48.8%

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-(3-methoxyphenyl)ethanol (32.5 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)-5-(4-(3-methoxyphenethoxy)phenyl)-2,6-dimethylpyridin-3-yl)acetic acid (11.9 mg, 0.021 mmol, 48.5% yield). 1H NMR (500 MHz, DMSO-d6) δ 7.26-7.18 (m, 2H), 7.07-6.98 (m, 3H), 6.94-6.87 (m, 2H), 6.82-6.78 (m, 1H), 5.81 (s, 1H), 4.31-4.17 (m, 2H), 3.31 (br. s., 2H), 3.04 (t, J=6.8 Hz, 2H), 2.86-2.76 (m, 1H), 2.43 (s, 3H), 2.16 (br. s., 1H), 2.05 (s, 3H), 1.98-1.92 (m, 1H), 1.50 (br. s., 1H), 1.36-1.23 (m, 1H), 1.17 (d, J=11.7 Hz, 1H), 1.12 (s, 9H), 1.02 (d, J=14.7 Hz, 1H), 0.85 (s, 3H), 0.61 (s, 3H). 2H of piperidine were not resolved. LCMS (M+H)=575.5.

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-831dfbd927a0438e8028b38fdf3d44e5
Source dataset
uspto-grants-2015_11
Patent number
US09193720B2

Reaction notes

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