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

HRID 1873161Notes

Reaction equation

HRID 1873161 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 9896671(S)-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 53886340(S)-2-[2,6-Dibromo-4-(6-bromo-benzo[b]naphtho[2,3-d]thiophen-11-yl)-phenoxy]-3-phenyl-propionic acidYield 63%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Aqueous potassium hydroxide (1 N, 2.40 mL, 2.40 mmol) was added to a stirred solution of (S)-2-[2,6-dibromo-4-(6-bromo-benzo[b]naphtho[2,3-d]thiophen-11 -yl)-phenoxy]-3-phenyl-propionic acid, methyl ester (0.88 g, 1.21 mmol) in THF (12 mL)/methanol (8 mL). After 2 h the solution was concentrated, diluted with water (50 mL) and acidified with 10% aqueous HCl. The reaction mixture was then partitioned between water and ether. The ether phase was concentrated and triturated with ether and pet. ether. It was then recrystalized from methanol to provide the title compound as a white solid (0.54 g, 63%): [a]D25 =-24.81° (10.08 mg/mL CHCl3); NMR (CDCl3); δ8.36 (d, J=8 Hz, 1 H), 7.81 (d, J=8 Hz, 1 H), 7.68 (ddd, J=8, 5, 3 Hz, 1 H), 7.58 (dd, J=10, 2 Hz, 2 H), 7.54-7.48 (m, 2 H), 7.44-7.27 (m, 6 H), 7.16 (ddd, J=8, 7, 1), 6.72 (d, J=8 Hz, 1 H), 5.45 (t, J=7 Hz, 1 H), 3.59 (d, J=7 Hz, 2 H); MS (EI): [M+], 3 bromine isotope pattern, 708 (24%), 710 (80%) 712 (100%) 714 (40%); Anal. Calc. for C31H19Br3O3S: C, 52.35, H, 2.69, N, 0.00. Found: C, 52.05, 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 pL; 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 (50 mL)
  3. customThe reaction mixture was then partitioned between water and ether
  4. concentrationThe ether phase was concentrated
  5. customtriturated with ether and pet. ether
  6. customIt was then recrystalized from methanol

Sources & evidence

ORD record
ord-9e77b0d5a1254087a223f473406dadfc
Source dataset
uspto-grants-2000_08
Patent number
US06110962

Reaction notes

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