Acetic Acid → HCID 782859, compound

HRID 480645Notes

Reaction equation

HRID 480645 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[F:10])[CH:5]=O.C(O)(=O)C.[NH:15]1[CH2:20][CH2:19][O:18][CH2:17][CH2:16]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[Br:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[F:10])[CH2:5][N:15]1[CH2:20][CH2:19][O:18][CH2:17][CH2:16]1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 8083MorpholineHCID 1736043-Bromo-4-fluorobenzaldehydeHCID 5049666Sodium triacetoxyborohydride

Product 1

HCID 782859HCID 782859, compoundYield 72%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

A solution of 3-bromo-4-fluorobenzaldehyde (50.0 g) in 1,2-dichloroethane (500 mL) is cooled to 0° C. Acetic acid (14.1 mL) and morpholine (23.6 mL) are added slowly, maintaining the temperature below 4° C. Sodium triacetoxyborohydride (78.3 g) is added all at once, maintaining the temperature below 5° C. The mixture is allowed to warm to rt and stirred for 18 hrs. The reaction is quenched with 1 N NaOH (200 mL) and extracted with CH2Cl2 (500 mL). The organic layer is washed with 1 N NaOH (2×200 mL). The aqueous layers are combined and back-extracted with CH2Cl2 (100 mL). The organic layers are combined and extracted with 0.5 N HCl (5×250 mL). The acidic aqueous layers are combined, and 2 N NaOH is added until the solution is basic (pH=12). The aqueous layer is then extracted with CH2Cl2 (6×100 mL). The organic layers are combined, dried (MgSO4) and concentrated in vacuo to a clear, colorless oil. The crude product is distilled (126° C., 0.3 Torr) to afford 48.9 g (72%) of the title compound as a clear, colorless oil. Physical characteristics: B.p. 126° C. (0.3 Torr); 1H NMR (300 MHz, DMSO-d6) δ 7.62, 7.35-7.29, 3.56, 3.45, 2.34; 13C NMR (75 MHz, DMSO-d6) δ 157.3, 136.1, 133.3, 129.8, 116.2, 107.7, 66.1, 60.9, 53.0; IR (liq.) 2855, 2807, 1495, 1455, 1348, 1257, 1244, 1118, 1009, 862 cm−1; MS (ESI+) m/z 274 (M+H)+. Anal. Calcd for C11H13BrFNO: C, 48.20; H, 4.78; N, 5.11; Br, 29.15. Found: C, 48.04; H, 4.79; N, 5.11; Br, 28.18.

Workup

  1. temperaturemaintaining the temperature below 4° C
  2. temperaturemaintaining the temperature below 5° C
  3. customThe reaction is quenched with 1 N NaOH (200 mL)
  4. extractionextracted with CH2Cl2 (500 mL)
  5. washThe organic layer is washed with 1 N NaOH (2×200 mL)
  6. extractionback-extracted with CH2Cl2 (100 mL)
  7. extractionextracted with 0.5 N HCl (5×250 mL)
  8. addition2 N NaOH is added until the solution
  9. extractionThe aqueous layer is then extracted with CH2Cl2 (6×100 mL)
  10. dry with materialdried (MgSO4)
  11. concentrationconcentrated in vacuo to a clear, colorless oil
  12. distillationThe crude product is distilled (126° C., 0.3 Torr)

Sources & evidence

ORD record
ord-6ddef3e011a9415ca98121df46bf359e
Source dataset
uspto-grants-2003_11
Patent number
US06653307B2

Reaction notes

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