Triphenylphosphine → HCID 86755715, compound

HRID 1873214Notes

Reaction equation

HRID 1873214 reaction equation
[Br:1][C:2]1[C:14]2[S:13][C:12]3[CH:15]=[CH:16][CH:17]=[CH:18][C:11]=3[C:10]=2[C:9]([C:19]2[C:20]([F:27])=[C:21]([OH:26])[C:22]([F:25])=[CH:23][CH:24]=2)=[C:8]2[C:3]=1[CH:4]=[CH:5][CH:6]=[CH:7]2.[C:28]([O:33][CH3:34])(=[O:32])[C@H:29]([CH3:31])O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CCOC(/N=N/C(OCC)=O)=O>C1C=CC=CC=1.C(Cl)Cl>[Br:1][C:2]1[C:14]2[S:13][C:12]3[CH:15]=[CH:16][CH:17]=[CH:18][C:11]=3[C:10]=2[C:9]([C:19]2[C:20]([F:27])=[C:21]([C:22]([F:25])=[CH:23][CH:24]=2)[O:26][C@H:29]([CH3:31])[C:28]([O:33][CH3:34])=[O:32])=[C:8]2[C:3]=1[CH:4]=[CH:5][CH:6]=[CH:7]2

Participants

7

Reactant 4

HCID 11776TriphenylphosphineHCID 94386methyl (S)-lactateHCID 5462977Diethyl azodicarboxylateHCID 18687831HCID 18687831, compound

Product 1

HCID 86755715HCID 86755715, compoundYield 86%

Reagents, catalysts & solvents 2

HCID 241BenzeneSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 3-(6-bromo-benzo[b]naphtho[2,3-d]thiophen-11-yl)-2,6 difluoro-phenol (0.570 g, 1.29 mmol), commercially available (S)-lactic acid, methyl ester. (0.246 mL, 2.58 mmol) and triphenylphosphine (0.677g, 2.58 mmol) in dry benzene (7 mL) was added diethylazodicarboxylate (0.406 mL, 2.58 mmol) dropwise at room temperature under a dry nitrogen atmosphere. The reaction mixture was sealed in a pressure bottle and immersed in a pre-heated oil bath at 105° C. After heating for 2.5 hours the mixture was stirred at ambient temperature for about 14 hours. The reaction mixture was then diluted with methylene chloride and combined with silica gel. The solvents were removed and the adsorbate was flash chromatographed (90/10 petroleum ether/ethyl acetate) to give (R)-2-[3-(6-bromo-benzo[b]naphtho[2,3-d ]thiophen-11-yl)-2,6-difluoro-phenoxy]-propionic acid, methyl ester as a white solid (0.59 g, 86%). To a solution of this methyl ester (0.46 g, 0.929 mmol) in tetrahydrofuran (18 mL) and methanol (6 mL) was added a 1 N aqueous solution of potassuim hydroxide (1.39 mL, 1.39 mmol) dropwise at room temperature. After stirring for 2 hours the solvents were removed and the residue was combined with water (50 mL) and acidified with 10% HCl. The solid was extracted into ether. The layers were shaken together well, separated, and the organic layer was washed with water and concentrated to give the title compound as a white solid (0.396 g, 88%): [a]D25=+13.22 (9.383 mg/mL methanol); NMR (400 MHz, DMSO-d6): δ13.11 (s, 1 H), 8.31 (d, J=8 Hz, 1H), 8.10-8.08 (m, 1H), 7.83-7.78 (m, 1H), 7.65-7.46 (m, 4 H), 7.32-7.19 (m, 2 H), 6.82-6.75 (m, 1 H), 4.98-4.93 (m, 1 H), 1.53-1.50 (m, 3 H); MS (-FAB): (M-H): one bromine pattern observed: 511/513 (2%); Anal. Calc. for C25H15BrF2O3S: C, 58.49, H, 2.95, N, 0.00. Found: C, 58.41, H, 3.44, N, 0.02.

Workup

  1. customThe reaction mixture was sealed in a pressure bottle
  2. customimmersed in a pre-heated oil bath at 105° C
  3. temperatureAfter heating for 2.5 hours the mixture
  4. customThe solvents were removed
  5. customchromatographed (90/10 petroleum ether/ethyl acetate)

Sources & evidence

ORD record
ord-e1154c4c1d3549e3b5dcddd2d725945d
Source dataset
uspto-grants-2000_08
Patent number
US06110962

Reaction notes

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