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4-Nitrobenzylamine hydrochloride → (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(4-nitrobenzylcarbamoyloxy)ethyl)pyridine 1-oxide

HRID 1776462
Notes
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Reaction equation

HRID 1776462 reaction equation
[Cl:1][C:2]1[CH:3]=[N+:4]([O-:39])[CH:5]=[C:6]([Cl:38])[C:7]=1[CH2:8][C@@H:9]([C:23]1[CH:28]=[CH:27][C:26]([O:29][CH:30]([F:32])[F:31])=[C:25]([O:33][CH2:34][CH:35]2[CH2:37][CH2:36]2)[CH:24]=1)[O:10][C:11](OC1C=CC([N+]([O-])=O)=CC=1)=[O:12].Cl.[N+:41]([C:44]1[CH:49]=[CH:48][C:47]([CH2:50][NH2:51])=[CH:46][CH:45]=1)([O-:43])=[O:42]>C(Cl)Cl.CN(C1C=CN=CC=1)C>[Cl:38][C:6]1[CH:5]=[N+:4]([O-:39])[CH:3]=[C:2]([Cl:1])[C:7]=1[CH2:8][C@@H:9]([C:23]1[CH:28]=[CH:27][C:26]([O:29][CH:30]([F:31])[F:32])=[C:25]([O:33][CH2:34][CH:35]2[CH2:37][CH2:36]2)[CH:24]=1)[O:10][C:11](=[O:12])[NH:51][CH2:50][C:47]1[CH:46]=[CH:45][C:44]([N+:41]([O-:43])=[O:42])=[CH:49][CH:48]=1
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

5

Reactant 2

HCID 112524674-Nitrobenzylamine hydrochlorideHCID 86679418(S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((4-nitrophenoxy)-carbonyloxy)ethyl)pyridine 1-oxide

Product 1

HCID 86679419(S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(4-nitrobenzylcarbamoyloxy)ethyl)pyridine 1-oxideYield 86.1%

Reagents, catalysts & solvents 2

HCID 14284
4-(Dimethylamino)pyridine
Catalyst
HCID 6344DichloromethaneSolvent2×

Procedure

To a stirred solution of compound (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((4-nitrophenoxy)-carbonyloxy)ethyl)pyridine 1-oxide, (227 mg, 0.388 mmol) in DCM (10 ml), (4-nitrophenyl)methanamine hydrochloride (88 mg, 0.465 mmol), and DMAP (56.9 mg, 0.465 mmol) were added. The reaction mixture was stirred at RT overnight. After 20 hours, the mixture was diluted with DCM and washed with a solution of K2CO3. he organic layer was dried over Na2SO4, evaporated and the resulting crude was purified by flash chromatography on silica gel (DCM:MeOH 10:0.3) affording the desired product (200 mg, 0.334 mmol, 86% yield, MS/ESI+ 598.3 [MH]+).

Workup

  1. waitAfter 20 hours
  2. washwashed with a solution of K2CO3
  3. dry with materialhe organic layer was dried over Na2SO4
  4. customevaporated
  5. customthe resulting crude was purified by flash chromatography on silica gel (DCM:MeOH 10:0.3)

Sources & evidence

ORD record
ord-c53770f542cc4830a83d9b53dd8c0f96
Source dataset
uspto-grants-2016_02
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US09265768B2

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes