Ammonia → {(S)-6-[(R)-7-Fluoro-4-(3-methoxybenzyl)-indan-1-yloxy]-2,3-dihydrobenzofuran-3-yl}-acetic acid methyl ester

HRID 2406521Notes

Reaction equation

[CH3:1][O:2][C:3](=[O:26])[CH2:4][C@H:5]1[C:9]2[CH:10]=[CH:11][C:12]([O:14][C@H:15]3[C:23]4[C:18](=[C:19](Br)[CH:20]=[CH:21][C:22]=4[F:24])[CH2:17][CH2:16]3)=[CH:13][C:8]=2[O:7][CH2:6]1.[Cl-].[CH3:28][O:29][C:30]1[CH:31]=[C:32]([CH:35]=[CH:36][CH:37]=1)[CH2:33][Zn+].Cl.N>[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.O1CCCC1>[CH3:1][O:2][C:3](=[O:26])[CH2:4][C@H:5]1[C:9]2[CH:10]=[CH:11][C:12]([O:14][C@H:15]3[C:23]4[C:18](=[C:19]([CH2:33][C:32]5[CH:35]=[CH:36][CH:37]=[C:30]([O:29][CH3:28])[CH:31]=5)[CH:20]=[CH:21][C:22]=4[F:24])[CH2:17][CH2:16]3)=[CH:13][C:8]=2[O:7][CH2:6]1

Participants

Conditions

Temperature: 60 °C

Procedure

The title compound is prepared from {(S)-6-[(R)-4-bromo-7-fluoro-indan-1-yloxy]-2,3-dihydro-benzofuran-3-yl}-acetic acid methyl ester (84 mg), 3-methoxy-benzylzinc chloride (0.5 mol/L in tetrahydrofuran, 1.2 mL) and tetrakis(triphenylphosphine)-palladium (23 mg). Degassed tetrahydrofuran (1 mL) is added under Ar atmosphere, and the mixture is heated to 60° C. and shaken at this temperature overnight. The mixture is acidified with 4 N aqueous hydrochloric acid (1 mL) and then neutralized with saturated aqueous ammonia solution. The organic phase is separated, diluted with N,N-dimethylformamide (1 mL), and purified by HPLC on reversed phase (MeCN/water) to give the title compound. LC (method 6): tR=1.17 min.

Workup

customThe organic phase is separated
additiondiluted with N,N-dimethylformamide (1 mL)
custompurified by HPLC on reversed phase (MeCN/water)

Sources & evidence

ORD record: ord-7ed164b9c7bc4b11b3b29d6c887aff54
Source dataset: uspto-grants-2014_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08809376B2

Reaction notes

Loading…