Ethyl Acetate → HCID 67348341, compound

HRID 237280Notes

Reaction equation

HRID 237280 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:15]=[CH:16][CH:17]=1)[CH2:5][O:6][C:7]1[CH:12]=[CH:11][C:10]([F:13])=[CH:9][C:8]=1[OH:14].[H-].[Na+].[C:20]([O:24][C:25]([N:27]1[CH2:31][CH2:30][CH:29](OC2C=CC(Cl)=CC=2C=O)C1)=[O:26])([CH3:23])([CH3:22])[CH3:21].CCOC(C)=O>CN(C=O)C.O>[C:20]([O:24][C:25]([N:27]1[CH2:31][CH:30]([O:14][C:8]2[CH:9]=[C:10]([F:13])[CH:11]=[CH:12][C:7]=2[O:6][CH2:5][C:4]2[CH:15]=[CH:16][CH:17]=[C:2]([Cl:1])[CH:3]=2)[CH2:29]1)=[O:26])([CH3:21])([CH3:22])[CH3:23]

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 24758Sodium hydrideHCID 67346490HCID 67346490, compoundHCID 87086903HCID 87086903, compound

Product 1

HCID 67348341HCID 67348341, compoundYield 124.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Conditions

Temperature
50 °C

Procedure

To the title compound of Step B (200 mg, 0.79 mmol) in DMF (5.0 mL) was added 60 wt % NaH (34.3 mg, 0.86 mmol). The mixture was heated to 50° C. for 1 h then cooled to rt and 3-methanesulfonyloxy-azetidine-1-carboxylic acid tert-butyl ester (Example 90 Step A, 229 mg, 0.91 mmol) in DMF was added. This mixture was heated to 80° C. for 18 h, cooled to rt and treated with EtOAc (50 mL) and H2O (100 mL). The organic layer was separated, washed with H2O (2×50 mL) and dried to give a solid (400 mg). This solid was purified on RP HPLC to yield the title compound (90 mg, 28%). 1H NMR (CDCl3) 7.44 (s, 1H), 7.36-7.23 (m, 3H), 6.86 (dd, J=8.9, 5.4 Hz, 1H), 6.60 (dd, J=8.0, 2.9 Hz, 1H), 6.33 (dd, J=9.6, 2.9 Hz, 1H), 5.03 (s, 2H), 4.90-4.80 (m, 1H), 4.33-4.22 (m, 2H), 4.07-4.02 (m, 2H), 1.54-1.28 (m, 9H).

Workup

  1. temperaturethen cooled to rt
  2. temperatureThis mixture was heated to 80° C. for 18 h
  3. temperaturecooled to rt
  4. customThe organic layer was separated
  5. washwashed with H2O (2×50 mL)
  6. customdried

Sources & evidence

ORD record
ord-59d3070615e84efd9f2296663b45f4e2
Source dataset
uspto-grants-2014_02
Patent number
US08642583B2

Reaction notes

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