Tributylphosphine → {(S)-6-[(R)-4-bromo-5-trifluoromethyl-indan-1-yloxy]-2,3-dihydro-benzofuran-3-yl}-acetic acid methyl ester

HRID 1422611Notes

Reaction equation

HRID 1422611 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[C:41]([C:42]([F:45])([F:44])[F:43])=[CH:40][CH:39]=[C:38]2[C:34]=1[CH2:35][CH2:36][C@@H:37]2O.C(P(CCCC)CCCC)CCC>O1CCCC1.O>[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])[C:41]([C:42]([F:43])([F:44])[F:45])=[CH:40][CH:39]=4)[CH2:35][CH2:36]3)=[CH:29][C:24]=2[O:23][CH2:22]1

Participants

7

Reactant 4

HCID 13831TributylphosphineHCID 97268Di-tert-butyl azodicarboxylateHCID 53393313(S)-Methyl 2-(6-hydroxy-2,3-dihydrobenzofuran-3-yl)acetateHCID 86700775(S)-4-bromo-5-trifluoromethyl-indan-1-ol

Product 1

HCID 86700774{(S)-6-[(R)-4-bromo-5-trifluoromethyl-indan-1-yloxy]-2,3-dihydro-benzofuran-3-yl}-acetic acid methyl ester

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of di-tert-butyl azodicarboxylate (6.3 g) in tetrahydrofuran (20 mL) is added dropwise over 45 min to a solution of [(S)-6-hydroxy-2,3-dihydro-benzofuran-3-yl]-acetic acid methyl ester (4.71 g), (S)-4-bromo-5-trifluoromethyl-indan-1-ol (6.00 g), and tri-n-butyl-phosphine (6.9 mL) in tetrahydrofuran (50 mL) at −10° C. The resulting solution is stirred in the cooling bath for 2.5 h and then diluted with water. The resulting mixture is extracted with ethyl acetate. The combined extracts 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 2): tR=0.85 min; Mass spectrum (ESI+): m/z=471/473 (Br) [M+H]+.

Workup

  1. extractionThe resulting mixture is extracted with ethyl acetate
  2. dry with materialThe combined extracts 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-8ad05c58da884a8f83c8393a0c9ee987
Source dataset
uspto-grants-2015_01
Patent number
US08927531B2

Reaction notes

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