Cesium carbonate → (1S,2S)-2-(4-{(R)-7-Fluoro-4-[4-(3-hydroxy-3-methyl-butoxy)-phenoxy]-indan-1-yloxy}-phenyl)-cyclopropanecarboxylic acid ethyl ester

HRID 625691Notes

Reaction equation

HRID 625691 reaction equation
[CH2:1]([O:3][C:4]([C@H:6]1[CH2:8][C@@H:7]1[C:9]1[CH:14]=[CH:13][C:12]([O:15][C@H:16]2[C:24]3[C:19](=[C:20]([O:26][C:27]4[CH:32]=[CH:31][C:30]([OH:33])=[CH:29][CH:28]=4)[CH:21]=[CH:22][C:23]=3[F:25])[CH2:18][CH2:17]2)=[CH:11][CH:10]=1)=[O:5])[CH3:2].[OH:34][C:35]([CH3:50])([CH3:49])[CH2:36][CH2:37]OS(C1C=CC(C)=CC=1)(=O)=O.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C)C=O.C(OCC)(=O)C>[CH2:1]([O:3][C:4]([C@H:6]1[CH2:8][C@@H:7]1[C:9]1[CH:10]=[CH:11][C:12]([O:15][C@H:16]2[C:24]3[C:19](=[C:20]([O:26][C:27]4[CH:32]=[CH:31][C:30]([O:33][CH2:37][CH2:36][C:35]([OH:34])([CH3:50])[CH3:49])=[CH:29][CH:28]=4)[CH:21]=[CH:22][C:23]=3[F:25])[CH2:18][CH2:17]2)=[CH:13][CH:14]=1)=[O:5])[CH3:2]

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 140012952-Methyl-4-[(4-methylbenzenesulfonyl)oxy]butan-2-ol2×HCID 118093735(1S,2S)-2-{4-[(R)-7-Fluoro-4-(4-hydroxy-phenoxy)-indan-1-yloxy]-phenyl}-cyclopropanecarboxylic acid ethyl ester2×

Product 1

HCID 118093710(1S,2S)-2-(4-{(R)-7-Fluoro-4-[4-(3-hydroxy-3-methyl-butoxy)-phenoxy]-indan-1-yloxy}-phenyl)-cyclopropanecarboxylic acid ethyl ester

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

(1S,2S)-2-{4-[(R)-7-Fluoro-4-(4-hydroxy-phenoxy)-indan-1-yloxy]-phenyl}-cyclopropanecarboxylic acid ethyl ester (Intermediate 7, 47 mg, 0.10 mmol), toluene-4-sulfonic acid 3-hydroxy-3-methyl-butyl ester (Intermediate 10, 54 mg, 0.21 mmol), and cesium carbonate (107 mg, 0.21 mmol) are suspended in dry N,N-dimethylformamide (2 mL) and stirred overnight. The mixture is diluted with ethyl acetate, washed with water, dried and the solvent removed. The residue is purified by flash chromatography (gradient of ethyl acetate in cyclohexane) to give the title compound. (Yield 60 mg). LC (METHOD 6): tR=0.75 min; Mass spectrum (ES+): m/z=535 [M+H]+.

Workup

  1. washwashed with water
  2. customdried
  3. customthe solvent removed
  4. customThe residue is purified by flash chromatography (gradient of ethyl acetate in cyclohexane)

Sources & evidence

ORD record
ord-1332b1d936584c288a0a5d28458bd02f
Source dataset
uspto-grants-2016_04
Patent number
US09308194B2

Reaction notes

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