Phosphoric Acid → HCID 178448633, compound

HRID 2410264Notes

Reaction equation

HRID 2410264 reaction equation
CC(C)([O-])C.[Na+].[CH3:7][O:8][CH2:9][O:10][C@H:11]([CH3:14])[CH2:12][OH:13].[CH2:15]([N:19]1[C:23]2[CH:24]=[N:25][CH:26]=[CH:27][C:22]=2[S:21]/[C:20]/1=[N:28]\[C:29](=[O:41])[C:30]1[CH:35]=[C:34]([C:36]([F:39])([F:38])[F:37])[CH:33]=[CH:32][C:31]=1F)[CH2:16][CH2:17][CH3:18].OP(O)(O)=O>O1CCCC1>[CH2:15]([N:19]1[C:23]2[CH:24]=[N:25][CH:26]=[CH:27][C:22]=2[S:21]/[C:20]/1=[N:28]\[C:29](=[O:41])[C:30]1[CH:35]=[C:34]([C:36]([F:39])([F:38])[F:37])[CH:33]=[CH:32][C:31]=1[O:13][CH2:12][C@H:11]([O:10][CH2:9][O:8][CH3:7])[CH3:14])[CH2:16][CH2:17][CH3:18]

Participants

6

Reactant 4

HCID 1004Phosphoric AcidHCID 10975472HCID 10975472, compoundHCID 23676156Sodium t-butoxideHCID 178448621HCID 178448621, compound

Product 1

HCID 178448633HCID 178448633, compoundYield 73.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
0 °C

Procedure

To a 250 mL three-necked flask were charged sodium tert-butoxide (97%, 0.69 g, 7.0 mmol), and anhydrous tetrahydrofuran (17 mL). The mixture was stirred, and cooled down to about 0° C. A solution of (R)-2-(methoxymethoxy)propan-1-ol (0.96 g, 8.0 mmol) in tetrahydrofuran (2.0 mL) was added slowly at the internal temperature <5° C. The solution was mixed at <5° C. for 30 minutes, followed by addition of the N-[(2Z)-3-butyl[1,3]thiazolo[4,5-c]pyridin-2(3H)-ylidene]-2-fluoro-5-(trifluoromethyl)benzamide (1.59 g, 4.0 mmol) from Part B of Example 1 in tetrahydrofuran (36 mL) at <0° C. The resulting mixture was stirred at about 0° C. for 4 hours or until less than 5% of starting material remains. 125 g of 1.5% H3PO4 aqueous solution was added slowly to the reaction mixture at <5° C. The resulting slurry was mixed at about 0° C. for 1 hour, and then allowed to warm up to room temperature. The slurry was stirred at room temperature for 5 hours, and the product collected by filtration. The wet cake was washed with water-acetonitrile (2:1) (20 mL), and dried under vacuum at 50° C. overnight with a slow flow of nitrogen to give a white solid (1.46 g, 73%). MS-ESI: 498 (M+1); 1H-NMR (DMSO-d6) δ 0.94 (3H, t, J=7.4 Hz), 1.24 (3H, d, J=5.9 Hz), 1.41 (2H, m), 1.81 (2H, m), 3.23 (3H, s), 4.08 (3H, m), 4.52 (2H, t, J=7.5 Hz), 4.60 (1H, d, J=6.6 Hz), 4.75 (1H, d, J=6.9 Hz), 7.28 (1H, d, J=8.8 Hz), 7.75 (1H, d, J=8.8 Hz), 7.94 (1H, d, J=5.2 Hz), 8.24 (1H, d, J=2.2 Hz), 8.44 (1H, d, J=5.2 Hz), 8.95 (1H, s). 13C-NMR (CDCl3-DMSO-d6) δ 13.51, 17.28, 19.51, 29.28, 45.17, 54.50, 70.16, 72.23, 94.42, 113.39, 117.32, 120.10 (q, J=33 Hz, C—CF3), 123.66 (q, J=268 Hz, CF3), 126.05, 127.62, 128.75, 132.90, 133.14, 134.36, 142.71, 159.70, 164.56, 172.26.

Workup

  1. additionThe solution was mixed at <5° C. for 30 minutes
  2. additionThe resulting slurry was mixed at about 0° C. for 1 hour
  3. temperatureto warm up to room temperature
  4. stirringThe slurry was stirred at room temperature for 5 hours
  5. filtrationthe product collected by filtration
  6. washThe wet cake was washed with water-acetonitrile (2:1) (20 mL)
  7. customdried under vacuum at 50° C. overnight with a slow flow of nitrogen

Sources & evidence

ORD record
ord-a516cb92ae8746a197bb955ab0b27301
Source dataset
uspto-grants-2014_08
Patent number
US08816086B2

Reaction notes

Loading…