4-Methylmorpholine → HCID 21035288, compound

HRID 1832116Notes

Reaction equation

HRID 1832116 reaction equation
[NH2:1][C:2]1[CH:27]=[CH:26][C:5]([CH2:6][N:7]2[C:12]([CH3:13])=[CH:11][C:10]([O:14][CH2:15][C:16]3[CH:21]=[CH:20][C:19]([F:22])=[CH:18][C:17]=3[F:23])=[C:9]([Br:24])[C:8]2=[O:25])=[CH:4][CH:3]=1.CN1CCOCC1.[C:35]([O:38][C@@H:39]([CH3:43])[C:40](Cl)=[O:41])(=[O:37])[CH3:36].CN=C=O>ClCCl>[C:35]([O:38][CH:39]([CH3:43])[C:40]([NH:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][N:7]2[C:12]([CH3:13])=[CH:11][C:10]([O:14][CH2:15][C:16]3[CH:21]=[CH:20][C:19]([F:22])=[CH:18][C:17]=3[F:23])=[C:9]([Br:24])[C:8]2=[O:25])=[CH:26][CH:27]=1)=[O:41])(=[O:37])[CH3:36]

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 12228Methyl IsocyanateHCID 11094804(1S)-2-Chloro-1-methyl-2-oxoethyl acetateHCID 22051042HCID 22051042, compound

Product 1

HCID 21035288HCID 21035288, compoundYield 99%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a reaction vessel (borosilicate culture tube) was added compound of Example 611 (0.300 g, 0.69 mmol) and dichloromethane (3.0 mL). A stock solution of N-methylmorpholine (0.30 M, 3.0 mL) was added and the parallel reaction apparatus was then orbitally shaken (Labline Benchtop Orbital Shaker) at approximately 200 RPM at room temperature for 10 minutes. (S)-(−)-2-Acetoxypropionyl chloride (0.131 mL, 1.04 mmol) was then added to the reaction vessel and the reaction apparatus was orbitally shaken at room temperature for 1.5 hours. At this time the reaction was diluted with dichloromethane (20 mL) and treated with approximately 2.1 g of polyamine resin (2.63 mmol/g) and approximately 3.8 g of methylisocyanate fucntionalized polystyrene (1.10 mmol/g) and the orbital shaking was continued at 200 RPM at room temperature overnight. The reaction vessel was then opened and the solution Phase products were separated from the insoluble quenched byproducts by filtration and collection into a vial. After partial evaporation the insoluble byproducts were rinsed with dichloromethane (2×10 mL). The filtrate was evaporated by blowing N2 over the vial to afford an off-white solid (0.375 g, 99%). 1H NMR (400 MHz, DMF-d6) δ 10.14 (s, 1H), 7.75 (app dt, J=6.98, 8.59 Hz, 1H), 7.67-7.64 (m, 2H), 7.30 (ddd, J=2.55, 9.26, 11.81 Hz, 1H), 7.21-7.17 (m, 3H), 6.61 (s, 1H), 5.37 (s, 4H), 5.11 (q, J=6.85 Hz, 1H), 2.40 (s, 3H), 2.10 (s, 3H), 1.46 (d, J=6.85 Hz, 3H). ES-HRMS m/z 549.0790 (M+H calcd for C25H23BrF2N2O5 requires 549.0831).

Workup

  1. stirringthe reaction apparatus was orbitally shaken at room temperature for 1.5 hours
  2. stirringthe orbital shaking
  3. waitwas continued at 200 RPM at room temperature overnight
  4. customthe solution Phase products were separated from the insoluble quenched byproducts by filtration and collection into a vial
  5. customAfter partial evaporation the insoluble byproducts
  6. washwere rinsed with dichloromethane (2×10 mL)
  7. customThe filtrate was evaporated

Sources & evidence

ORD record
ord-048d1196bf8f4abfa862671fa788a675
Source dataset
uspto-grants-2006_06
Patent number
US07067540B2

Reaction notes

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