Water → HCID 22625792, compound

HRID 1637816Notes

Reaction equation

HRID 1637816 reaction equation
[OH2:1].[NH2:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2([CH3:13])[CH2:12][NH:11][CH2:10]2)=[C:5]([F:14])[CH:4]=1.[CH2:15]([O:22][C:23](Cl)=[O:24])[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1>CC(C)=O.C(=O)(O)[O-].[Na+]>[C:23]([N:11]1[CH2:10][C:9]([C:6]2[CH:7]=[CH:8][C:3]([NH:2][C:23]([O:22][CH2:15][C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)=[O:1])=[CH:4][C:5]=2[F:14])([CH3:13])[CH2:12]1)([O:22][CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)=[O:24]

Participants

6

Reactant 3

HCID 962WaterHCID 10387Benzyl chloroformate2×HCID 15481020HCID 15481020, compound

Product 1

HCID 22625792HCID 22625792, compound

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 516892Sodium BicarbonateSolvent3×

Conditions

Temperature
0 °C

Procedure

A 500 mL round bottom flask equipped with a magnetic spinbar and addition funnel was charged with 85 mL water, 38.4 g sodium bicarbonate (0.46 mol) and a solution of 9.82 g 3-(4-amino-2-fluorophenyl)-3-methylazetidine (0.051 mol theory) in 165 mL acetone. The resulting orange suspension was cooled to 0° C. and treated with 43 mL benzylchloroformate (0.30 mol) with gas evolution and the reaction turning a light yellow color. The cooling bath was removed and the reaction mixture was stirred at room temperature for 65 hours. TLC indicates incomplete consumption of the starting aminoaniline and an additional 12.8 g sodium bicarbonate (0.15 mol) and 14 mL benzylchloroformate (0.10 mol) was added with additional gas evolution. After two hours, the reaction mixture was diluted with 350 mL saturated sodium bicarbonate and extracted three times with ethyl acetate (300 mL). The combined organics were washed once with water (200 mL), once with brine (200 mL), dried over MgSO4, filtered, and concentrated to give 29.86 g of a light yellow oil. This crude material was purified by LC on 850 g (230-400) silica gel eluting with 25% ethyl acetate/hexanes to afford 11.67 g (51%) of the title compound as a light yellow solid. Rf 0.18 (25% ethyl acetate/hexanes); IR (neat) 1735, 1707, 1693, 1600, 1534, 1455, 1424, 1414, 1221, 1081 cm-1 ; 1H NMR (300 MHz, CDCl3) δ7.35 (m, 11H, aromatic), 6.96 (m, 3H, aromatic & NH), 5.19 (s, 2H, Ph-CH2), 5.09 (s, 2H, Ph-CH2), 4.30 (d, 2H, J=8.2 Hz, N--CH2a s), 4.00 (d, 2H, J=8.4 Hz, N--CH2b s), 1.59 (s, 3H, CH3); 13C NMR (75 MHz, CDCl3) 160.4 (d, JCF =245 Hz), 156.6, 153.0, 138.1 (d, JCF =11 Hz), 136.5, 135.7, 128.6, 128.4, 128.2, 127.9, 127.8, 127.5, 127.0, 126.9, 113.9, 106.6 (d, JCF =27 Hz), 67.1, 66.6, 60.8, 60.2, 36.1, 28.2; Anal. Calcd for C26H25N2O4F1 : C, 69.63; H, 5.62; N, 6.25. Found: C, 69.37; H, 5.69; N, 5.87.

Workup

  1. customA 500 mL round bottom flask equipped with a magnetic spinbar and addition funnel
  2. customThe cooling bath was removed
  3. customconsumption of the starting aminoaniline
  4. waitAfter two hours
  5. extractionextracted three times with ethyl acetate (300 mL)
  6. washThe combined organics were washed once with water (200 mL), once with brine (200 mL)
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-0574c4a513114ebf9e4cd0d9480d1aee
Source dataset
uspto-grants-2000_03
Patent number
US06043266

Reaction notes

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