Methanol → (R)-2-[2,6-Dibromo-4-(6-bromo-benzo[b]naphtho[2,3-d]thiophen-11-yl)-phenoxy]-3-phenyl-propionic acid

HRID 1873159Notes

Reaction equation

HRID 1873159 reaction equation
[OH-].[K+].[Br:3][C:4]1[CH:22]=[C:21]([C:23]2[C:32]3[C:33]4[CH:39]=[CH:38][CH:37]=[CH:36][C:34]=4[S:35][C:31]=3[C:30]([Br:40])=[C:29]3[C:24]=2[CH:25]=[CH:26][CH:27]=[CH:28]3)[CH:20]=[C:19]([Br:41])[C:5]=1[O:6][C@H:7]([CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[C:8]([O:10]C)=[O:9].CO>C1COCC1>[Br:3][C:4]1[CH:22]=[C:21]([C:23]2[C:32]3[C:33]4[CH:39]=[CH:38][CH:37]=[CH:36][C:34]=4[S:35][C:31]=3[C:30]([Br:40])=[C:29]3[C:24]=2[CH:25]=[CH:26][CH:27]=[CH:28]3)[CH:20]=[C:19]([Br:41])[C:5]=1[O:6][C@H:7]([CH2:12][C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1)[C:8]([OH:10])=[O:9]

Participants

5

Reactant 3

HCID 887MethanolHCID 14797Potassium HydroxideHCID 11803003(R)-2-[2,6-Dibromo-4-(6-bromo-benzo[b]naphtho[2,3-d]thiophen-11-yl)-phenoxy]-3-phenyl-propionic acid, methyl ester

Product 1

HCID 9810403(R)-2-[2,6-Dibromo-4-(6-bromo-benzo[b]naphtho[2,3-d]thiophen-11-yl)-phenoxy]-3-phenyl-propionic acidYield 67%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Aqueous potassium hydroxide (1 N, 6.37 mL, 6.37 mmol) was added to a stirred solution of (R)-2-[2,6-dibromo-4-(6-bromo-benzo[b]naphtho[2,3-d]thiophen-11 -yl)-phenoxy]-3-phenyl-propionic acid, methyl ester (2.31 g, 3.19 mmol) in THF (22 mL)/methanol (15 mL). After 2 h the solution was concentrated, diluted with water (100 mL) and acidified with 10% aqueous HCl. The solid was filtered, washed with water and triturated with petroleum ether. It was then recrystalyzed from methanol to provide the title compound as a white solid (1.52 g, 67%): mp 140-142° C.: [a]D25=+25.66 (10.52 mg/mL CHCl3); NMR (DMSO-d6);δ13.26 (broad s, 1 H), 8.29 (d, J=8 Hz, 1 H), 8.07 (d, J=8 Hz, 1 H), 7.80 (m, 1 H), 7.79 (dd, J=7, 3 Hz, 2 H), 7.63 (ddd, J=8, 7, 1 Hz, 1 H), 7.55 (d, J=8 Hz, 1 H), 7.51 (ddd, J=8, 7, 1 Hz, 1 H), 7.41 (d, J=7 Hz, 2 H), 7.38-7.32 (m, 3 H), 7.31-7.22 (m, 3 H), 6.64 (d, J=8 Hz, 1 H), 5.32 (t, J =7 Hz, 1 H), 3.41 (d, J=7 Hz, 2 H); MS (EI): [M+], 3 bromine isotope pattern, 708 (35%), 710 (90%) 712 (100%) 714 (40%); Anal. Calc. for C31H19Br3O3S: C, 52.35, H, 2.69, N, 0.00. Found: C, 52.46, H, 2.59, N, 0.10. Chiral analytical HPLC determined that this compound had approx. 100% EE [column:Chirobiotic V, 5 micron (4.6 ×250 mm); isocratic, 1:1 ethanol:hexane; flow rate =0.80 mL/min; injection volume =0.3 μL; sample conc. =0.25 mg/mL; retention time, R-enantiomer =21 min; retention time, S-enantiomer =16 min⟧

Workup

  1. concentrationAfter 2 h the solution was concentrated
  2. additiondiluted with water (100 mL)
  3. filtrationThe solid was filtered
  4. washwashed with water
  5. customtriturated with petroleum ether

Sources & evidence

ORD record
ord-9b417160c91d495bb46c48b469ac47cb
Source dataset
uspto-grants-2000_08
Patent number
US06110962

Reaction notes

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