Ammonia → HCID 66886103, compound

HRID 2204049Notes

Reaction equation

HRID 2204049 reaction equation
[CH2:1]([O:8][C@H:9]([C@@H:29]([O:50][CH2:51][C:52]1[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=1)[C@H:30]([O:42][CH2:43][C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1)[C:31](=O)[CH2:32][O:33][CH2:34][C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)[C:10]([C:12]1[CH:17]=[CH:16][C:15]([Cl:18])=[C:14]([CH2:19][C:20]2[CH:25]=[CH:24][C:23]([O:26][CH2:27][CH3:28])=[CH:22][CH:21]=2)[CH:13]=1)=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.N.C([BH3-])#[N:60].[Na+]>CO.ClCCl>[CH2:43]([O:42][C@H:30]1[C@H:29]([O:50][CH2:51][C:52]2[CH:53]=[CH:54][CH:55]=[CH:56][CH:57]=2)[C@@H:9]([O:8][CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)[CH:10]([C:12]2[CH:17]=[CH:16][C:15]([Cl:18])=[C:14]([CH2:19][C:20]3[CH:21]=[CH:22][C:23]([O:26][CH2:27][CH3:28])=[CH:24][CH:25]=3)[CH:13]=2)[NH:60][CH:31]1[CH2:32][O:33][CH2:34][C:35]1[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=1)[C:44]1[CH:45]=[CH:46][CH:47]=[CH:48][CH:49]=1

Participants

6

Reactant 3

HCID 222AmmoniaHCID 5003444Sodium cyanoborohydrideHCID 66884581HCID 66884581, compound

Product 1

HCID 66886103HCID 66886103, compoundYield 35.4%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of compound from step C (400 mg, 0.5 mmol), 7N ammonia in MeOH (1.0 mL) and freshly activated 4 Å molecular sieves (250 mg) in dichloromethane (20 mL) were refluxed overnight. The reaction mixture was cooled to room temperature, then sodium cyanoborohydride (160 mg, 2.55 mmol) was added and refluxed for additional 2 h. The reaction mixture was filtered, diluted with dichloromethane (20 mL), washed with water, brine, dried (sodium sulfate), and concentrated under reduced pressure. Chromatography on silica gel (50 to 100% acetonitrile containing 0.1% ammonium acetate/water gradient) provided (3R,4R,5S)-3,4,5-tris(benzyloxy)-2-(benzyloxymethyl)-6-(4-chloro-3-(4-ethoxybenzyl)phenyl)piperidine (136 mg, 34%).

Workup

  1. temperaturerefluxed for additional 2 h
  2. filtrationThe reaction mixture was filtered
  3. additiondiluted with dichloromethane (20 mL)
  4. washwashed with water, brine
  5. dry with materialdried (sodium sulfate)
  6. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-00745400edb340db8dd2a29e331bd554
Source dataset
uspto-grants-2016_06
Patent number
US09365602B2

Reaction notes

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