Potassium Phosphate, Tribasic → 4-[4-(Azetidine-1-carbonyl)-phenoxy]-2,2-dimethyl-2,3-dihydro-benzofuran-6-carboxylic acid methyl ester

HRID 1643571Notes

Reaction equation

HRID 1643571 reaction equation
[O-]P([O-])([O-])=O.[K+].[K+].[K+].[CH3:9][O:10][C:11]([C:13]1[CH:23]=[C:22]([OH:24])[C:16]2[CH2:17][C:18]([CH3:21])([CH3:20])[O:19][C:15]=2[CH:14]=1)=[O:12].[N:25]1([C:29]([C:31]2[CH:36]=[CH:35][C:34](Br)=[CH:33][CH:32]=2)=[O:30])[CH2:28][CH2:27][CH2:26]1>C1(C)C=CC=CC=1.CC([O-])=O.CC([O-])=O.[Pd+2].C(P(C(C)(C)C)C1C=CC=CC=1C1C(C(C)C)=CC(C(C)C)=CC=1C(C)C)(C)(C)C>[CH3:9][O:10][C:11]([C:13]1[CH:23]=[C:22]([O:24][C:34]2[CH:33]=[CH:32][C:31]([C:29]([N:25]3[CH2:26][CH2:27][CH2:28]3)=[O:30])=[CH:36][CH:35]=2)[C:16]2[CH2:17][C:18]([CH3:21])([CH3:20])[O:19][C:15]=2[CH:14]=1)=[O:12]

Participants

7

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 25067323Methyl 4-hydroxy-2,2-dimethyl-2,3-dihydro-1-benzofuran-6-carboxylateHCID 595603461-(4-Bromobenzoyl)azetidine

Product 1

HCID 595602514-[4-(Azetidine-1-carbonyl)-phenoxy]-2,2-dimethyl-2,3-dihydro-benzofuran-6-carboxylic acid methyl esterYield 72.5%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 11618717Di-tert-butyl(2',4',6'-tris(propan-2-yl)-(1,1'-biphenyl)-2-yl)phosphaneCatalystHCID 1140TolueneSolvent

Conditions

Temperature
110 °C

Procedure

K3PO4 (1.23 g, 5.79 mmol), Pd(OAc)2 (41 mg, 0.81 mmol) and 2-di-t-butylphosphino-2′,4′6′-tri-i-propyl-1,1′-biphenyl (68 mg, 0.16 mmol) was added to a solution of 4-hydroxy-2,2-dimethyl-2,3-dihydro-benzofuran-6-carboxylic acid methyl ester (3e) (646 mg, 2.91 mmol) and azetidin-1-yl-(4-bromo-phenyl)-methanone (35a) (697 mg, 2.90 mmol) in toluene (10 mL). The reaction mixture was heated to 110° C. overnight. The mixture was filtered, washed with EtOAc, and concentrated. The residue was purified by flash column chromatograph eluting with 10-25 % EtOAc in hexanes to give a white solid (802 mg, 72% yield). 1H NMR (400 MHz, CDCl3) δ 7.64 (d, J=6.82 Hz, 2 H) 7.23 (s, 1 H) 7.20 (s, 1 H) 6.97 (d, J=7.33 Hz, 2 H) 4.24-4.34 (m, 4 H) 3.87 (s, 3 H) 2.88 (s, 2 H) 2.50-2.61 (m, 1 H) 2.32-2.42 (m, 1H) 1.47 (s, 6 H); LCMS for C22H23NO5 m/z 382.00 (M+H)+.

Workup

  1. filtrationThe mixture was filtered
  2. washwashed with EtOAc
  3. concentrationconcentrated
  4. customThe residue was purified by flash column chromatograph
  5. washeluting with 10-25 % EtOAc in hexanes

Sources & evidence

ORD record
ord-ff357e1501ca4aad84c4272fc8a4d80c
Source dataset
uspto-grants-2012_02
Patent number
US08119624B2

Reaction notes

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