Toluene → HCID 67348192, compound

HRID 237282Notes

Reaction equation

HRID 237282 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:11][CH:10]([O:12][C:13]2[CH:18]=[C:17](Br)[CH:16]=[CH:15][C:14]=2[O:20][CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[C:24]([Cl:28])[CH:23]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[S:29]1[CH:33]=[CH:32][C:31](B(O)O)=[CH:30]1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].C1(C)C=CC=CC=1>C(Cl)Cl.CC(P(C(C)(C)C)[C-]1C=CC=C1)(C)C.C1C=CC([C-]2C(C3C=CC=CC=3)=C(C3C=CC=CC=3)C(C3C=CC=CC=3)=C2C2C=CC=CC=2)=CC=1.[Fe+2].C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd]>[C:1]([O:5][C:6]([N:8]1[CH2:11][CH:10]([O:12][C:13]2[CH:18]=[C:17]([C:31]3[CH:32]=[CH:33][S:29][CH:30]=3)[CH:16]=[CH:15][C:14]=2[O:20][CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[C:24]([Cl:28])[CH:23]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

8

Reactant 4

HCID 1140TolueneHCID 62657Potassium Phosphate, TribasicHCID 581760Thiophene-3-boronic acidHCID 67347456HCID 67347456, compound

Product 1

HCID 67348192HCID 67348192, compound

Reagents, catalysts & solvents 3

HCID 6505921(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladiumCatalystHCID 129828017Ditert-butyl(cyclopenta-2,4-dien-1-yl)phosphane;iron(2+);(2,3,4,5-tetraphenylcyclopenta-1,4-dien-1-yl)benzeneCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
80 °C

Procedure

3-[5-Bromo-2-(3-chloro-benzyloxy)-phenoxy]-azetidine-1-carboxylic acid tert-butyl ester (188 mg, 0.4 mmol), 3-thiophene boronic acid (53 mg, 0.41 mmol), Q-Phos (23 mg, 0.032 mmol), Pd(dba)2 (9.2 mg, 0.016 mmol) and K3PO4 (255 mg, 1.2 mmol) were taken into toluene (3 mL) and heated at 80° C. After the reaction was complete it was cooled to rt, diluted with CH2Cl2 (20 mL), filtered, washed with H2O (2×25 mL) and concentrated to give 3-[2-(3-chloro-benzyloxy)-5-thiophen-3-yl-phenoxy]-azetidine-1-carboxylic acid tert-butyl ester. To this compound was added MeOH (10 mL) followed by 4M HCl in dioxane (4 mL). After 4 h the reaction was concentrated and purified on RP HPLC (basic) to yield the title compound (12 mg). MS (ESI): mass calcd. for C20H18ClNO2S, 371.9; m/z found, 372.2 [M+H]+. 1H NMR (CDCl3): 10.30-9.57 (m, 1H), 7.43 (s, 1H), 7.40-7.28 (m, 6H), 7.24 (dd, J=8.4, 2.1 Hz, 1H), 7.01 (d, J=2.1 Hz, 1H), 6.96 (d, J=8.5 Hz, 1H), 5.24-4.99 (m, 3H), 4.40-4.11 (m, 4H).

Workup

  1. temperaturewas cooled to rt
  2. filtrationfiltered
  3. washwashed with H2O (2×25 mL)
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-d5bc926e3a45429d9bec88cf4eeb674d
Source dataset
uspto-grants-2014_02
Patent number
US08642583B2

Reaction notes

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