Glycine → HCID 59594400, compound

HRID 1186060Notes

Reaction equation

HRID 1186060 reaction equation
N#N.[NH2:3][CH2:4][C:5]([OH:7])=O.[Cl:8][C:9]1[CH:29]=[CH:28][C:12]2[N:13]([CH2:19][C:20]3[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[CH:22][CH:21]=3)C(=O)[O:15][C:16](=O)[C:11]=2[CH:10]=1>CC(O)=O>[Cl:8][C:9]1[CH:29]=[CH:28][C:12]2[N:13]([CH2:19][C:20]3[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[CH:22][CH:21]=3)[C:5](=[O:7])[CH2:4][NH:3][C:16](=[O:15])[C:11]=2[CH:10]=1

Participants

5

Reactant 3

HCID 750GlycineHCID 947NitrogenHCID 59594378HCID 59594378, compound

Product 1

HCID 59594400HCID 59594400, compoundYield 39%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
130 °C

Procedure

In a 2 L RBF equipped with mechanical stir, condenser and N2 inlet, glycine (34 g, 0.45 mol) was added to 6-chloro-1-(4-methoxybenzyl)-1H-benzo[d][1,3]oxazine-2,4-dione (280 g) followed by the addition of AcOH (500 mL). Reaction flask was heated in a 130° C. oil bath for 8 h. Solvent was removed on the rotary evaporator at 50-60° C. To the thick syrupy crude product was added heptane (1 L) and H2O (1 L) followed by the addition of NaHCO3 to adjust the pH to ˜8-9. The mixture gave a solid along with organic and aqueous layers. The organic and aqueous layers were decanted and the solid was slurried with 500 mL of 5% NaHCO3 solution. NaHCO3 layer was decant and sticky solid was suspended in 700 mL EtOAc and 300 mL of dichloromethane (DCM). The mixture was stirred for 20 min, filtered and the filter cake was washed with 1 L of DCM. The filtrate was concentrated and residue was pass through 330 g silica gel plug using 25/75 to 75/25 EtOAC/heptane (total of 8 L). Clean fractions were combined to give 58 g of pure product. An additional 13 g of ˜70% pure product was obtained from less pure fractions. Yield was 47% over two steps. 1H NMR (300 MHz, DMSO-d6) δ 3.45 (m, 1H), 3.6 (s, 3H), 3.8 (m, 1H), 4.8 (d, 1H), 5.3 (d, 1H), 6.8 (d, 2H), 7.1 (d, 2H), 7.7-7.5 (m, 3H), 8.9 (t, 1H).

Workup

  1. customReaction flask
  2. customSolvent was removed on the rotary evaporator at 50-60° C
  3. additionTo the thick syrupy crude product was added heptane (1 L) and H2O (1 L)
  4. additionfollowed by the addition of NaHCO3
  5. customThe mixture gave a solid along with organic and aqueous layers
  6. customThe organic and aqueous layers were decanted
  7. customNaHCO3 layer was decant
  8. filtrationfiltered
  9. washthe filter cake was washed with 1 L of DCM
  10. concentrationThe filtrate was concentrated

Sources & evidence

ORD record
ord-828499d6a3d04174b2c6e1dc94f5178a
Source dataset
uspto-grants-2014_03
Patent number
US08673897B2

Reaction notes

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