Triphenylphosphine → HCID 118307709, compound

HRID 718454Notes

Reaction equation

HRID 718454 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].[F:35][C:36]1[C:41]([F:42])=[CH:40][C:39]([F:43])=[C:38]([F:44])[C:37]=1[CH2:45][CH2:46][OH:47].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C.[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:47][CH2:46][CH2:45][C:37]3[C:36]([F:35])=[C:41]([F:42])[CH:40]=[C:39]([F:43])[C:38]=3[F: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

8

Reactant 5

HCID 11776TriphenylphosphineHCID 14798Sodium HydroxideHCID 5363146Diisopropyl azodicarboxylateHCID 55267363HCID 55267363, compoundHCID 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 118307709HCID 118307709, compoundYield 22.6%

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 (25 mg, 0.053 mmol), 2-(2,3,5,6-tetrafluorophenyl)ethanol (51.8 mg, 0.267 mmol) and Ph3P-resin (69.7 mg, 0.267 mmol) in THF (2 mL) was added DIAD (0.052 mL, 0.267 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-(2,3,5,6-tetrafluorophenethoxy)phenyl)pyridin-3-yl)acetic acid (7.4 mg, 0.012 mmol, 22.49% yield). 1H NMR (500 MHz, DMSO-d6) δ 7.48 (br. s., 1H), 7.21 (d, J=8.4 Hz, 1H), 7.08-6.88 (m, 3H), 5.81 (s, 1H), 4.34-4.20 (m, 2H), 3.29 (br. s., 1H), 3.13 (t, J=6.4 Hz, 2H), 2.82-2.76 (m, 1H), 2.43 (s, 3H), 2.16 (br. s., 1H), 2.04 (s, 3H), 1.94 (br. s., 1H), 1.48 (br. s., 1H), 1.29 (br. s., 1H), 1.17 (d, J=13.2 Hz, 1H), 1.12 (s, 9H), 1.00 (d, J=11.0 Hz, 1H), 0.84 (br. s., 3H), 0.59 (br. s., 3H). LCMS+H)=617.2.

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-be86f8edb68a4eb69c8ad6f4b197526e
Source dataset
uspto-grants-2015_11
Patent number
US09193720B2

Reaction notes

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