Tributylphosphine → {(S)-6-[(R)-4-bromo-7-fluoro-indan-1-yloxy]-2,3-dihydro-benzofuran-3-yl}-acetic acid methyl ester

HRID 2408527Notes

Reaction equation

HRID 2408527 reaction equation
N(C(OC(C)(C)C)=O)=NC(OC(C)(C)C)=O.[CH3:17][O:18][C:19](=[O:31])[CH2:20][C@H:21]1[C:25]2[CH:26]=[CH:27][C:28]([OH:30])=[CH:29][C:24]=2[O:23][CH2:22]1.[Br:32][C:33]1[CH:41]=[CH:40][C:39]([F:42])=[C:38]2[C:34]=1[CH2:35][CH2:36][C@@H:37]2O.C(P(CCCC)CCCC)CCC.C([O-])(O)=O.[Na+]>O1CCCC1>[CH3:17][O:18][C:19](=[O:31])[CH2:20][C@H:21]1[C:25]2[CH:26]=[CH:27][C:28]([O:30][C@H:37]3[C:38]4[C:34](=[C:33]([Br:32])[CH:41]=[CH:40][C:39]=4[F:42])[CH2:35][CH2:36]3)=[CH:29][C:24]=2[O:23][CH2:22]1

Participants

7

Reactant 5

HCID 13831TributylphosphineHCID 97268Di-tert-butyl azodicarboxylateHCID 516892Sodium BicarbonateHCID 53393313(S)-Methyl 2-(6-hydroxy-2,3-dihydrobenzofuran-3-yl)acetateHCID 86697104(S)-4-bromo-7-fluoro-2,3-dihydro-1H-inden-1-ol

Product 1

HCID 86697103{(S)-6-[(R)-4-bromo-7-fluoro-indan-1-yloxy]-2,3-dihydro-benzofuran-3-yl}-acetic acid methyl ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of di-tert-butyl azodicarboxylate (18.0 g) in tetrahydrofuran (80 mL) is added dropwise over 45 min to a solution of [(S)-6-hydroxy-2,3-dihydro-benzofuran-3-yl]-acetic acid methyl ester (11.0 g), (S)-4-bromo-7-fluoro-2,3-dihydro-1H-inden-1-ol (12.0 g) and tributylphosphine (19.3 mL) in tetrahydrofuran (320 mL) at −10° C. The resulting solution is stirred for 30 min and then poured into saturated aqueous NaHCO3 solution. The mixture is extracted with dichloromethane, and the combined organic phases are dried (MgSO4) and concentrated. The residue is chromatographed on silica gel (cyclohexane/ethyl acetate 90:10→70:30) to give the title compound. LC (method 1): tR=1.41 min; Mass spectrum (ESI+): m/z=421 [M+H]+.

Workup

  1. extractionThe mixture is extracted with dichloromethane
  2. dry with materialthe combined organic phases are dried (MgSO4)
  3. concentrationconcentrated
  4. customThe residue is chromatographed on silica gel (cyclohexane/ethyl acetate 90:10→70:30)

Sources & evidence

ORD record
ord-89777bc14d474855a2a7e8fee9a0d7b0
Source dataset
uspto-grants-2014_08
Patent number
US08815864B2

Reaction notes

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