Ammonium Chloride → HCID 178423625, compound

HRID 470661Notes

Reaction equation

HRID 470661 reaction equation
[NH2:1][C@H:2]1[CH2:7][CH2:6][C@H:5]([OH:8])[CH2:4][CH2:3]1.[Cl:9][C:10]1[CH:18]=[C:17]2[C:13]([C@@:14]3([C:27]4([CH2:32][CH2:31][C:30]([CH3:34])([CH3:33])[CH2:29][CH2:28]4)[N:26]4[C@@H:21]([C:22](=[O:47])[O:23][C@@H:24]([C:41]5[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=5)[C@H:25]4[C:35]4[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=4)[C@@H:20]3[C:48]3[CH:53]=[CH:52][CH:51]=[C:50]([Cl:54])[C:49]=3[F:55])[C:15](=[O:19])[NH:16]2)=[CH:12][CH:11]=1.[Cl-].[NH4+]>O1CCCC1>[Cl:9][C:10]1[CH:18]=[C:17]2[C:13]([C:14]3([C@@H:20]([C:48]4[CH:53]=[CH:52][CH:51]=[C:50]([Cl:54])[C:49]=4[F:55])[C@H:21]([C:22]([NH:1][C@H:2]4[CH2:7][CH2:6][C@H:5]([OH:8])[CH2:4][CH2:3]4)=[O:47])[N:26]([C@H:25]([C:35]4[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=4)[C@@H:24]([OH:23])[C:41]4[CH:42]=[CH:43][CH:44]=[CH:45][CH:46]=4)[C:27]43[CH2:28][CH2:29][C:30]([CH3:34])([CH3:33])[CH2:31][CH2:32]4)[C:15](=[O:19])[NH:16]2)=[CH:12][CH:11]=1

Participants

5

Reactant 3

HCID 25517Ammonium ChlorideHCID 70872025(3'S,4'R,7'S,8'S,8a'R)-6''-chloro-8'-(3-chloro-2-fluorophenyl)-4,4-dimethyl-3',4'-diphenyl-3',4',8',8a'-tetrahydro-1'H-dispiro[cyclohexane-1,6'-pyrrolo[2,1-c][1,4]oxazine-7',3''-indole]-1',2''(1''H)-dioneHCID 178511715HCID 178511715, compound

Product 1

HCID 178423625HCID 178423625, compoundYield 101.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Trans-4-aminocyclohexanol (167 mg, 1.45 mmol) was added to a tetrahydrofuran (10 ml) solution of the compound (194 mg, 0.29 mmol) obtained in Step 1 above and the resulting mixture was heated to reflux for 6 days. After cooling, saturated ammonium chloride solution was added, followed by extraction with ethyl acetate. The organic layer was washed with brine and then dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure and the residue was purified by silica gel column chromatography [chloroform:methanol=100:0→30:1 (v/v)] to give 230 mg (100%) of the title compound as a pale yellow amorphous solid.

Workup

  1. temperaturewas heated
  2. temperatureto reflux for 6 days
  3. temperatureAfter cooling
  4. extractionfollowed by extraction with ethyl acetate
  5. washThe organic layer was washed with brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. customThe solvent was evaporated under reduced pressure
  8. customthe residue was purified by silica gel column chromatography [chloroform:methanol=100:0→30:1 (v/v)]

Sources & evidence

ORD record
ord-cf2c73dae4c74c8380bede9d332945eb
Source dataset
uspto-grants-2014_01
Patent number
US08629133B2

Reaction notes

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