Water → HCID 25008470, compound

HRID 2093198Notes

Reaction equation

HRID 2093198 reaction equation
[F:1][C:2]([F:49])([F:48])[C:3]1[CH:4]=[C:5]([C@H:13]2[O:17][C:16](=[O:18])[N:15]([CH2:19][C:20]3[CH:25]=[C:24]([C:26]([F:29])([F:28])[F:27])[CH:23]=[CH:22][C:21]=3[C:30]3[CH:31]=[C:32]([C:37]4[CH:42]=[CH:41][C:40]([C:43](O)=[O:44])=[CH:39][C:38]=4[CH3:46])[CH:33]=[CH:34][C:35]=3[Cl:36])[C@H:14]2[CH3:47])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.B.CCOC(C)=O.CCCCCC.O>C1COCC1>[F:49][C:2]([F:1])([F:48])[C:3]1[CH:4]=[C:5]([C@H:13]2[O:17][C:16](=[O:18])[N:15]([CH2:19][C:20]3[CH:25]=[C:24]([C:26]([F:27])([F:29])[F:28])[CH:23]=[CH:22][C:21]=3[C:30]3[C:35]([Cl:36])=[CH:34][CH:33]=[C:32]([C:37]4[CH:42]=[CH:41][C:40]([CH2:43][OH:44])=[CH:39][C:38]=4[CH3:46])[CH:31]=3)[C@H:14]2[CH3:47])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1

Participants

6

Reactant 4

HCID 962WaterHCID 6331BoraneHCID 21226206Ethyl acetate hexaneHCID 57704777HCID 57704777, compound

Product 1

HCID 25008470HCID 25008470, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of acid from Example 34 (1.0 g, 1.40 mmol) in THF (15 ml) at −78° C., Borane (2.79 ml, 2.79 mmol, 1M solution in THF) was added. The solution was stirred at −78° C. for 30 min and slowly warmed to room temperature for 2 h. TLC showed no more starting material (EtOAc/hexane 3:7). Water (10 ml) was added. The mixture was extracted with EtOAc (3×20 ml). The combined EtOAc layers were washed with saturated sodium bicarbonate, brine and dried over sodium sulfate. The solvent was removed and the residue was purified by flash column on silica gel, eluting with EtOAc/hexane (30:70) to give the title compound as a colorless solid. 1H NMR (CDCl3, 500 MHz): δ a mixture of 1:1 atopoisomers 7.89 (s, 1H), 7.73 (s, 1H), 7.72 (s, 2H), 7.70 (m, 1H), 7.59 (d, J=8.0 Hz, 1H), 7.49 (d, J=8.5 Hz, 0.5H), 7.47 (d, J=8.0 Hz, 0.5H), 7.39-7.36 (m, 2H), 7.32 (s, 1H), 7.25 (m 1.5H), 7.20 (d, J=2.0 Hz, 0.5H), 5.62 (d, J=8.0 Hz, 1H), 4.99 (d, J=15.0 Hz, 0.5H), 4.83 (d, J=16.0 Hz, 0.5H), 4.73 (s, 2H), 4.15 (s, 1H), 4.10 (d, J=16.0 Hz, 0.5H), 4.01 (d, J=15.5 Hz, 0.5H), 3.96 (m, 0.5H), 3.86(m, 0.5H), 2.34 (s, 1.5H), 2.33 (s, 1.5H), 0.61 (d, J=6.5 Hz, 1.5H), 0.58 (d, J=6.5 Hz, 1.5H).

Workup

  1. temperatureslowly warmed to room temperature for 2 h
  2. extractionThe mixture was extracted with EtOAc (3×20 ml)
  3. washThe combined EtOAc layers were washed with saturated sodium bicarbonate, brine
  4. dry with materialdried over sodium sulfate
  5. customThe solvent was removed
  6. customthe residue was purified by flash column on silica gel
  7. washeluting with EtOAc/hexane (30:70)

Sources & evidence

ORD record
ord-1915ec6d93b34bb8888475418f3926c2
Source dataset
uspto-grants-2013_05
Patent number
US08440702B2

Reaction notes

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