Triphenylphosphine → HCID 118307736, compound

HRID 718456Notes

Reaction equation

HRID 718456 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][C:36]1[C:40]([CH2:41][CH2:42][OH:43])=[C:39]([CH3:44])[O:38][N:37]=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C>C1COCC1>[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:40]3[C:36]([CH3:35])=[N:37][O:38][C:39]=3[CH3:44])=[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

6

Reactant 4

HCID 11776TriphenylphosphineHCID 5363146Diisopropyl azodicarboxylateHCID 127623462-(3,5-Dimethyl-1,2-oxazol-4-yl)ethan-1-olHCID 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 118307736HCID 118307736, compoundYield 41.6%

Reagents, catalysts & solvents 1

HCID 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 (50 mg, 0.107 mmol), 2-(3,5-dimethylisoxazol-4-yl)ethanol (75 mg, 0.533 mmol) and Ph3P-resin (139 mg, 0.533 mmol) in THF (2 mL) was added DIAD (0.104 mL, 0.533 mmol) at rt. After 18 h, mixture was filtered to remove polymer, concentrated and treated with 1NNaOH (1.067 mL, 1.067 mmol) in MeOH (2 mL) at 75° C. for 16 h. Mixture was then cooled and purified by prep-HPLC to afford (S)-2-(tert-butoxy)-2-(5-(4-(2-(3,5-dimethylisoxazol-4-yl)ethoxy)phenyl)-4-(4,4-dimethylpiperidin-1-yl)-2,6-dimethylpyridin-3-yl)acetic acid (25 mg, 0.044 mmol, 41.6% yield). 1H NMR (500 MHz, DMSO-d6) δ 7.20 (d, J=8.8 Hz, 1H), 7.07-6.92 (m, 3H), 5.75 (s, 1H), 4.17-4.01 (m, 2H), 3.41 (br. s., 1H), 3.17 (s, 2H), 2.79 (t, J=6.2 Hz, 2H), 2.42 (s, 3H), 2.34 (s, 3H), 2.21 (s, 3H), 2.17 (d, J=12.5 Hz, 1H), 2.06-2.02 (m, 2H), 1.93 (br. s., 1H), 1.49 (br. s., 1H), 1.29 (br. s., 1H), 1.16 (d, J=13.6 Hz, 1H), 1.11 (s, 9H), 1.01 (d, J=9.9 Hz, 1H), 0.84 (br. s., 3H), 0.61 (br. s., 3H). LCMS (M+H)=564.4.

Workup

  1. filtrationmixture was filtered
  2. customto remove polymer
  3. concentrationconcentrated
  4. additiontreated with 1NNaOH (1.067 mL, 1.067 mmol) in MeOH (2 mL) at 75° C. for 16 h
  5. temperatureMixture was then cooled
  6. custompurified by prep-HPLC

Sources & evidence

ORD record
ord-f0ad1eda54f6435bbf0bb5fc9a919851
Source dataset
uspto-grants-2015_11
Patent number
US09193720B2

Reaction notes

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