Dichloromethane → 3-(4-Carboxy-2'-trifluoromethyl-biphenyl-3-yloxy)-azetidine-1-carboxylic acid tert-butyl ester

HRID 2038458Notes

Reaction equation

HRID 2038458 reaction equation
C(Cl)Cl.[C:4]([O:8][C:9]([N:11]1[CH2:14][CH:13]([O:15][C:16]2[CH:17]=[C:18]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=3[C:30]([F:33])([F:32])[F:31])[CH:19]=[CH:20][C:21]=2[CH:22]=[O:23])[CH2:12]1)=[O:10])([CH3:7])([CH3:6])[CH3:5].C1C=C(Cl)C=C(C(OO)=[O:42])C=1>CCOC(C)=O>[C:4]([O:8][C:9]([N:11]1[CH2:12][CH:13]([O:15][C:16]2[CH:17]=[C:18]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=3[C:30]([F:33])([F:31])[F:32])[CH:19]=[CH:20][C:21]=2[C:22]([OH:42])=[O:23])[CH2:14]1)=[O:10])([CH3:7])([CH3:5])[CH3:6]

Participants

5

Reactant 3

HCID 6344DichloromethaneHCID 70297m-Chloroperbenzoic acidHCID 873639173-(4-Formyl-2'-trifluoromethyl-biphenyl-3-yloxy)-azetidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 673442573-(4-Carboxy-2'-trifluoromethyl-biphenyl-3-yloxy)-azetidine-1-carboxylic acid tert-butyl esterYield 37.2%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To a CH2Cl2 (6 mL) solution of the title compound of Step A (0.236 g, 0.560 mmol) was added m-CPBA (77 wt %, 0.189 g, 0.840 mmol). After 15 h, 10% Na2S2O5 was added and the solution allowed to stir until the aqueous was KI paper negative and extracted with CH2Cl2 (2×). The combined organic layers were dried and treated with MeOH (10 mL) and 1N NaOH (10 mL). After 15 h, the reaction was partially concentrated to remove the MeOH and acidified with 1M HCl (220 mL) then extracted with EtOAc (2×). The combined organic layers were dried and concentrated. Silica gel chromatography (0-30% EtOAc in hexanes) gave 0.091 g (37% yield) of the title compound. (MS (ESI): mass calcd. for C22H22F3NO5, 437.15; m/z found, 382.1 [M-56]+, 460.1 [M+Na]+. 1H NMR (CDCl3): 7.73 (d, J=7.8 Hz, 1H), 7.55 (t, J=7.5 Hz, 1H), 7.45 (t, J=7.7 Hz, 1H), 7.32 (d, J=7.6 Hz, 1H), 6.99 (d, J=8.2 Hz, 1H), 6.87 (dd, J=8.2, 1.9 Hz, 1H), 6.52 (d, J=1.0 Hz, 1H), 4.97-4.88 (m, 1H), 4.30 (dd, J=9.8, 6.4 Hz, 2H), 4.05 (dd, J=9.9, 3.7 Hz, 2H), 1.45 (s, 9H)) and 0.091 g (39% yield) of 3-(4-Hydroxy-2′-trifluoromethyl-biphenyl-3-yloxy)-azetidine-1-carboxylic acid tert-butyl ester (MS (ESI): mass calcd. for C21H22F3NO4, 409.15; m/z found, 354.1 [M-56]+, 432.1 [M+Na]+. 1H NMR (CDCl3): 8.19 (d, J=8.0 Hz, 1H), 7.78 (d, J=8.2 Hz, 1H), 7.61 (t, J=7.2 Hz, 1H), 7.54 (t, J=7.5 Hz, 1H), 7.32 (d, J=7.5 Hz, 1H), 7.12 (dd, J=8.0, 1.3 Hz, 1H), 6.63 (s, 1H), 5.11-5.00 (m, 1H), 4.36 (dd, J=10.1, 6.4 Hz, 2H), 4.12 (dd, J=10.6, 3.6 Hz, 2H), 1.45 (s, 9H).

Workup

  1. extractionextracted with CH2Cl2 (2×)
  2. customThe combined organic layers were dried
  3. additiontreated with MeOH (10 mL) and 1N NaOH (10 mL)
  4. waitAfter 15 h
  5. concentrationthe reaction was partially concentrated
  6. customto remove the MeOH
  7. extractionthen extracted with EtOAc (2×)
  8. customThe combined organic layers were dried
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-71c88907100e47cea8a028a70941770f
Source dataset
uspto-grants-2013_11
Patent number
US08575364B2

Reaction notes

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