Water → HCID 67348174, compound

HRID 237275Notes

Reaction equation

HRID 237275 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:11][CH:10]([OH:12])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].[CH2:15]([O:22][C:23]1[C:28](F)=[CH:27][C:26]([Cl:30])=[CH:25][N:24]=1)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.O>CN1C(=O)CCC1.CCOC(C)=O>[C:1]([O:5][C:6]([N:8]1[CH2:11][CH:10]([O:12][C:28]2[C:23]([O:22][CH2:15][C:16]3[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=3)=[N:24][CH:25]=[C:26]([Cl:30])[CH:27]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 2756801Tert-butyl 3-hydroxyazetidine-1-carboxylateHCID 673497402-(Benzyloxy)-5-chloro-3-fluoropyridine

Product 1

HCID 67348174HCID 67348174, compoundYield 51.2%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 13387N-methyl-2-pyrrolidoneSolvent2×

Conditions

Temperature
50 °C

Procedure

To 3-hydroxy-azetidine-1-carboxylic acid tert-butyl ester (0.35 g, 2.0 mmol) in NMP (3 mL) was added 60% NaH in mineral oil (0.08 g, 2.0 mmol). After 20 min at rt, the reaction was heated to 50° C. for 20 min, cooled to rt and the title compound from step A (0.40 g, 1.7 mmol) in NMP (1 mL) was added. The reaction was then heated in a microwave reactor at 145° C. for 1 h, cooled to rt, poured into H2O and extracted with EtOAc (2×). The combined organics were washed with brine and dried. Silica gel chromatography (2-15% EtOAc in hexanes) gave 0.34 g (51% yield) of the title compound as a white solid. 1H NMR (CDCl3): 7.74 (d, J=2.1 Hz, 1H), 7.46 (d, J=7.0 Hz, 2H), 7.39-7.30 (m, 3H), 6.77 (d, J=2.1 Hz, 1H), 5.42 (s, 2H), 4.87-4.82 (m, 1H), 4.26 (dd, J=10.5, 6.4 Hz, 2H), 4.05 (dd, J=10.3, 4.2 Hz, 2H), 1.44 (s, 9H).

Workup

  1. temperaturecooled to rt
  2. temperatureThe reaction was then heated in a microwave reactor at 145° C. for 1 h
  3. temperaturecooled to rt
  4. extractionextracted with EtOAc (2×)
  5. washThe combined organics were washed with brine
  6. customdried

Sources & evidence

ORD record
ord-6da65b88fe29479bbd83510646050790
Source dataset
uspto-grants-2014_02
Patent number
US08642583B2

Reaction notes

Loading…