Triphenylphosphine → t-butyl-(S)-2-(2-(3-trifluoromethylphenyl)-4-((4-fluoro-N-methylphenylsulfonamido)methyl)phenoxy)propanate

HRID 68621Notes

Reaction equation

HRID 68621 reaction equation
[F:1][C:2]([F:30])([F:29])[C:3]1[CH:4]=[C:5]([C:9]2[CH:10]=[C:11]([CH:25]=[CH:26][C:27]=2[OH:28])[CH2:12][N:13]([CH3:24])[S:14]([C:17]2[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=2)(=[O:16])=[O:15])[CH:6]=[CH:7][CH:8]=1.[C:31]([O:35][C:36](=[O:40])[C@H:37](O)[CH3:38])([CH3:34])([CH3:33])[CH3:32].N(C(OCC)=O)=NC(OCC)=O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C1COCC1>[C:31]([O:35][C:36](=[O:40])[C@@H:37]([O:28][C:27]1[CH:26]=[CH:25][C:11]([CH2:12][N:13]([CH3:24])[S:14]([C:17]2[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=2)(=[O:16])=[O:15])=[CH:10][C:9]=1[C:5]1[CH:6]=[CH:7][CH:8]=[C:3]([C:2]([F:1])([F:29])[F:30])[CH:4]=1)[CH3:38])([CH3:34])([CH3:33])[CH3:32]

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 10953655tert-butyl (2R)-2-hydroxypropanoateHCID 66868277N-(3-(3-trifluoromethylphenyl)-4-hydroxybenzyl)-4-fluoro-N-methylbenzenesulfonamide

Product 1

HCID 66868551t-butyl-(S)-2-(2-(3-trifluoromethylphenyl)-4-((4-fluoro-N-methylphenylsulfonamido)methyl)phenoxy)propanateYield 13.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A solution of N-(3-(3-trifluoromethylphenyl)-4-hydroxybenzyl)-4-fluoro-N-methylbenzenesulfonamide (36) (50.0 mg, 0.114 mmol) and (R)-t-butyl-2-hydroxypropanoate (18.3 mg, 0.125 mmol, 1.1 eq, Chem-Impex International, Inc., Wood Dale, Ill., USA) in THF (2 mL) at 0° C. was added diethyl azodicarboxylate (20 μL, 0.125 mmol, 1.1 eq) and triphenylphosphine (33 mg 0.125 mmol, 1.1 eq). After stirring at 0° C. for 4 h the mixture was extracted between saturated sodium bicarbonate and ethyl acetate, dried (Na2SO4) and concentrated in vacuo. This crude product was purified on reversed phase semi-preparative HPLC to give 9 mg of t-butyl-(S)-2-(2-(3-trifluoromethylphenyl)-4-((4-fluoro-N-methylphenylsulfonamido)methyl)phenoxy)propanate. This intermediate was then dissolved in TFA/DCM (1 mL/1 mL) and stirred at room temperature for 30 min. Solvent was removed in vacuo and the residue was purified via reversed phase semi-preparative HPLC to afford 4.9 mg of (S)-2-(2-(3-trifluoromethylphenyl)-4-((4-fluoro-N-methylphenylsulfonamido)methyl)phenoxy)propanoic acid (Example 36). 1HNMR (CDCl3, 400 MHz): δ 7.84 (m, 3H), 7.70 (d, 1H), 7.56 (m, 2H), 7.26 (m, 3H), 7.20 (d, 1H), 6.88 (d, 1H), 4.80 (m, 1H), 4.15 (s, 2H), 2.64 (s, 3H), 1.57 (d, 3H). MS (ESI): MH+=512.1. HPLC (Method B) tR=2.78 min.

Workup

  1. extractionwas extracted between saturated sodium bicarbonate and ethyl acetate
  2. dry with materialdried (Na2SO4)
  3. concentrationconcentrated in vacuo
  4. customThis crude product was purified on reversed phase semi-preparative HPLC

Sources & evidence

ORD record
ord-760f0b6ef5da4d70bf572666894afa85
Source dataset
uspto-grants-2014_09
Patent number
US08822467B2

Reaction notes

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