Dichloromethane → cis-4-Benzyloxycarbonylamino-3-[(5-chloro-thiophene-2-carbonyl)-amino]-piperidine-1-carboxylic acid tert-butyl ester

HRID 1271720Notes

Reaction equation

HRID 1271720 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C@H:11]([NH:14][C:15]([O:17][CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[O:16])[C@H:10]([NH2:25])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Cl:26][C:27]1[S:31][C:30]([C:32](Cl)=[O:33])=[CH:29][CH:28]=1.CCN(CC)CC.C(Cl)Cl>CCOC(C)=O>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C@H:11]([NH:14][C:15]([O:17][CH2:18][C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=2)=[O:16])[C@H:10]([NH:25][C:32]([C:30]2[S:31][C:27]([Cl:26])=[CH:28][CH:29]=2)=[O:33])[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 8471TriethylamineHCID 5892235-Chlorothiophene-2-carbonyl ChlorideHCID 69440349tert-Butyl (3R,4S)-3-amino-4-{[(benzyloxy)carbonyl]amino}piperidine-1-carboxylate

Product 1

HCID 69443846cis-4-Benzyloxycarbonylamino-3-[(5-chloro-thiophene-2-carbonyl)-amino]-piperidine-1-carboxylic acid tert-butyl esterYield 37.1%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

Cis-3-amino-4-benzyloxycarbonylamino-piperidine-1-carboxylic acid tert-butyl ester (450 mg, 1.288 mmol), from Part F of Example 112, was added to a cooled mixture (0° C.) of 5-chloro-thiophen-carboxylic chloride (233 mg, 1.288 mmol), Et3N (0.54 mL, 3.864 mmol), and CH2Cl2 (10 mL). The mixture stirred overnight at rt. EtOAc (70 mL) was added. The mixture was washed with brine, and the organic phase dried over MgSO4 and concentrated. The crude product was purified by silica gel flash column chromatography (30% MeOH/EtOAc) to yield cis-4-benzyloxycarbonylamino-3-[(5-chloro-thiophene-2-carbonyl)-amino]-piperidine-1-carboxylic acid tert-butyl ester as a white solid (236 mg). LC-MS: (M-100): 394.

Workup

  1. washThe mixture was washed with brine
  2. dry with materialthe organic phase dried over MgSO4
  3. concentrationconcentrated
  4. customThe crude product was purified by silica gel flash column chromatography (30% MeOH/EtOAc)

Sources & evidence

ORD record
ord-ef6f8e86175043079530f03e055d0089
Source dataset
uspto-grants-2007_04
Patent number
US07205318B2

Reaction notes

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