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

HRID 2406507Notes

Reaction equation

HRID 2406507 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>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

6

Reactant 4

HCID 13831TributylphosphineHCID 97268Di-tert-butyl azodicarboxylateHCID 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 (for preparation see WO 2008001931; 11.0 g), (S)-4-bromo-7-fluoro-indan-1-ol (11.95 g), and tri-n-butyl-phosphine (19.3 mL) in tetrahydrofuran (320 mL) at −10° C. The resulting solution is stirred for 30 min and then partitioned between saturated aqueous NaHCO3 solution and dichloromethane. The aqueous phase is separated and extracted with dichloromethane. 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=421/423 (Br) [M+H]+.

Workup

  1. custompartitioned between saturated aqueous NaHCO3 solution and dichloromethane
  2. customThe aqueous phase is separated
  3. extractionextracted with dichloromethane
  4. dry with materialThe combined organic phases are dried (MgSO4)
  5. concentrationconcentrated
  6. customThe residue is chromatographed on silica gel (cyclohexane/ethyl acetate 90:10→70:30)

Sources & evidence

ORD record
ord-877c781ba7a74eb08f4ed9ed285be18a
Source dataset
uspto-grants-2014_08
Patent number
US08809376B2

Reaction notes

Loading…