Diphenylacetic Acid → HCID 118024062, compound

HRID 706375Notes

Reaction equation

HRID 706375 reaction equation
[NH2:1][CH:2]1[CH2:7][C@@H:6]([C:8]2[C:13]([F:14])=[CH:12][CH:11]=[C:10]([F:15])[C:9]=2[F:16])[C@@H:5]([CH3:17])[N:4]([CH2:18][C:19]([F:22])([F:21])[F:20])[C:3]1=[O:23].[C:24]1([CH:30]([C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)[C:31]([OH:33])=[O:32])[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1>C(OC(C)C)(=O)C.C1COCC1.ClC1C(O)=C(C=C(Cl)C=1)C=O>[C:24]1([CH:30]([C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)[C:31]([O-:33])=[O:32])[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1.[CH3:17][C@H:5]1[N:4]([CH2:18][C:19]([F:20])([F:22])[F:21])[C:3](=[O:23])[C@@H:2]([NH3+:1])[CH2:7][C@H:6]1[C:8]1[C:13]([F:14])=[CH:12][CH:11]=[C:10]([F:15])[C:9]=1[F:16]

Participants

6

Reactant 2

HCID 8333Diphenylacetic AcidHCID 89821845HCID 89821845, compound

Product 1

HCID 118024062HCID 118024062, compoundYield 91.4%

Reagents, catalysts & solvents 3

HCID 666603,5-DichlorosalicylaldehydeCatalystHCID 7915Isopropyl AcetateSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
57.5 °C

Procedure

To a mixture of crude material containing (5S,6R)-3-amino-6-methyl-1-(2,2,2-trifluoroethyl)-5-(2,3,6-trifluorophenyl)piperidin-2-one (24, 2.00 g, 5.88 mmol), prepared according to the same method as the previous example, and 3,5-dichloro-2-hydroxybenzaldehyde (0.011 g, 0.059 mmol) in isopropyl acetate (15.0 ml) at 55-60° C. under nitrogen was slowly added a solution of diphenylacetic acid (1.26 g, 5.88 mmol) in THF (10.0 ml) over 2 h. Upon completion of acid addition, a thick salt suspension was agitated at 55-60° C. for another 18 h and then was allowed to cool to ambient temperature. The salt was filtered and washed with isopropyl acetate. After drying at 60° C. in a vacuum oven with nitrogen purge for 8 hours, 25 (2.97 g, 91.4%) was obtained as crystals. 1H NMR (500 MHz, DMSO-d6): δ 7.48 (qd, J=9.4, 4.9 Hz, 1H), 7.32 (d, J=7.7 Hz, 4H), 7.25-7.26 (m, 4H), 7.19-7.17 (m, 3H), 6.79 (br, 3H), 4.95 (s, 1H), 4.67 (dq, J=15.3, 9.7 Hz, 1H), 3.81-3.79 (m, 3H), 3.62 (dd, J=11.6, 6.5 Hz, 1H), 2.66-2.62 (m, 1H), 2.25 (dd, J=12.9, 6.4 Hz, 1H), 1.11 (d, J=6.5 Hz, 3H); 13C NMR (100 MHz, DMSO-d6): δ 174.4, 171.8, 156.9 (ddd, J=244, 7.0, 2.5 Hz), 149.1 (ddd, J=249, 14.4, 8.5 Hz), 147.2 (ddd, J=246, 13.9, 3.2 Hz), 141.4, 129.0, 128.5, 126.7, 125.5 (q, J=281 Hz), 118.0 (dd, J=19.8, 13.8 Hz), 117.1 (dd, J=19.2, 10.6 Hz), 112.3 (ddd, J=26.1, 6.7, 3.3 Hz), 58.5, 57.1, 51.7, 44.8 (q, J=32.7 Hz), 35.3, 27.5 (br t, J=4.6 Hz), 14.5.

Workup

  1. additionTo a mixture of crude material
  2. customprepared
  3. additionUpon completion of acid addition
  4. temperatureto cool to ambient temperature
  5. filtrationThe salt was filtered
  6. washwashed with isopropyl acetate
  7. customAfter drying at 60° C. in a vacuum oven with nitrogen
  8. custompurge for 8 hours

Sources & evidence

ORD record
ord-e0ab1b2d57d84b8a9a0f5f5078d616cb
Source dataset
uspto-grants-2015_11
Patent number
US09174989B2

Reaction notes

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