Hydrochloric Acid → 2-[1,3,6,2]Dioxazaborocan-2-yl-4-trifluoromethyl-benzoic acid 2,2-dimethyl-propyl ester

HRID 1870568Notes

Reaction equation

HRID 1870568 reaction equation
[CH3:1][C:2]([CH3:18])([CH3:17])[CH2:3][O:4][C:5](=[O:16])[C:6]1[CH:11]=[CH:10][C:9]([C:12]([F:15])([F:14])[F:13])=[CH:8][CH:7]=1.[CH:19]([O:22][B:23](OC(C)C)[O:24][CH:25]([CH3:27])C)(C)[CH3:20].C([N-:35]C(C)C)(C)C.[Li+].Cl.N(CCO)CCO>O1CCCC1.O1CCCC1.CCCCCCC.C(O)(C)C>[CH3:1][C:2]([CH3:18])([CH3:17])[CH2:3][O:4][C:5](=[O:16])[C:6]1[CH:11]=[CH:10][C:9]([C:12]([F:13])([F:14])[F:15])=[CH:8][C:7]=1[B:23]1[O:24][CH2:25][CH2:27][NH:35][CH2:20][CH2:19][O:22]1

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 8113DiethanolamineHCID 21531Triisopropyl borateHCID 599219Neopentyl 4-(trifluoromethyl)benzoateHCID 2724682Lithium diisopropylamide

Product 1

HCID 107143722-[1,3,6,2]Dioxazaborocan-2-yl-4-trifluoromethyl-benzoic acid 2,2-dimethyl-propyl esterYield 74%

Reagents, catalysts & solvents 3

HCID 3776IsopropanolSolventHCID 8028TetrahydrofuranSolventHCID 21263495Tetrahydrofuran heptaneSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 4-trifluoromethyl-benzoic acid 2,2-dimethyl-propyl ester (35.8 g, 138 mmol) in tetrahydrofuran (250 mL) was added triisopropylborate (73.0 mL, 316 mmol). The solution was cooled to 0° C., lithium diisopropylamide (73.0 mL of a 2.0M solution in tetrahydrofuran/heptane, 146.0 mmol) was added dropwise over 20 minutes, and the red solution was stirred for an additional 30 minutes. Hexanes (200 mL) was added followed by 1N hydrochloric acid (200 mL). The mixture was stirred for 10 minutes and poured into hexanes (200 mL). The organic layer was washed with 1N hydrochloric acid (two times 150 mL), and brine (100 mL). The organic extracts were dried over magnesium sulfate, filtered, and concentrated to about 200 mL. Isopropyl alcohol (100 mL), and diethanolamine (15.95 g, 151.7 mmol) were added, and the mixture was stirred at room temperature for 10 hours. The solids were filtered and washed with a mixture of isopropyl alcohol (15 mL) and hexanes (30 mL) to provide 2-[1,3,6,2]dioxazaborocan-2-yl-4-trifluoromethyl-benzoic acid 2,2-dimethyl-propyl ester (37.83 g, 74% yield) as a white solid. mp=233-234° C; IR 3077, 2963, 2862, 1722, 1480, 1467, 1371, 1331, 1298, 1290, 1279, 1254, 1161, 1117, 1108, 1087, 1074, 995, 952, 862, cm-1, 1H NMR (400 MHz, CDCl3) δ 8.23 (s, 1H), 7.72 (d, J=7.9 Hz, 1H), 7.52 (dd, J=7.9, 1.3 Hz, 1H), 6.33 (brs, 1H), 4.08-4.14 (m, 2H), 3.98 (s, 2H), 3.93-3.98 (m, 2H), 3.42-3.50 (m, 2H), 2.88-2.94 (m, 2H), 1.02 (s, 9H); 13C NMR (100 MHz, CDCl3) 26.51, 31.69, 50.92, 63.33, 74.72, 123.94, 128.59, 132.06, 139.61, 171.56.

Workup

  1. stirringThe mixture was stirred for 10 minutes
  2. washThe organic layer was washed with 1N hydrochloric acid (two times 150 mL), and brine (100 mL)
  3. dry with materialThe organic extracts were dried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated to about 200 mL
  6. stirringthe mixture was stirred at room temperature for 10 hours
  7. filtrationThe solids were filtered
  8. washwashed with a mixture of isopropyl alcohol (15 mL) and hexanes (30 mL)

Sources & evidence

ORD record
ord-2b6332b282bf43deb4a5cb991df82d2d
Source dataset
uspto-grants-2000_08
Patent number
US06096906

Reaction notes

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