Triethylamine → tert-Butyl [(3S)-3-(ethoxymethyl)-3-(4-[4-(trifluoromethyl)pyridin-2-yl]piperazin-1-ylcarbonyl)cyclopentyl]carbamate

HRID 1261697Notes

Reaction equation

HRID 1261697 reaction equation
[C:1]([O:5][C:6]([NH:8][CH:9]1[CH2:13][CH2:12][C@:11]([CH2:17][O:18][CH2:19][CH3:20])([C:14]([OH:16])=O)[CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl.Cl.[F:23][C:24]([F:38])([F:37])[C:25]1[CH:30]=[CH:29][N:28]=[C:27]([N:31]2[CH2:36][CH2:35][NH:34][CH2:33][CH2:32]2)[CH:26]=1.C(N(CC)CC)C.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1>CN(C=O)C.C(Cl)Cl>[CH2:19]([O:18][CH2:17][C@:11]1([C:14]([N:34]2[CH2:35][CH2:36][N:31]([C:27]3[CH:26]=[C:25]([C:24]([F:38])([F:23])[F:37])[CH:30]=[CH:29][N:28]=3)[CH2:32][CH2:33]2)=[O:16])[CH2:12][CH2:13][CH:9]([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:2])([CH3:3])[CH3:4])[CH2:10]1)[CH3:20]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 685975881-[4-(Trifluoromethyl)pyridin-2-yl]piperazine dihydrochlorideHCID 68610943(1S)-3-[(tert-Butoxycarbonyl)amino]-1-(ethoxymethyl)cyclopentanecarboxylic acid

Product 1

HCID 86633372tert-Butyl [(3S)-3-(ethoxymethyl)-3-(4-[4-(trifluoromethyl)pyridin-2-yl]piperazin-1-ylcarbonyl)cyclopentyl]carbamateYield 40.7%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

(1S)-3-[(tert-Butoxycarbonyl)amino]-1-(ethoxymethyl)cyclopentanecarboxylic acid (429.4 mg, 1.494 mmol), 1-[4-(trifluoromethyl)pyridin-2-yl]piperazine dihydrochloride (500.0 mg, 1.644 mmol), triethylamine (0.833 mL, 5.98 mmol) and O-(benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (850.3 mg, 2.242 mol) (HBTU) were mixed in dry DMF (10.2 mL). The resulting brown solution was stirred at room temperature under N2 overnight. The reaction mixture was diluted with CH2Cl2 and washed with saturated Na2CO3. The aqueous layer was extracted with CH2Cl2 four times. The combined organic layers were dried (MgSO4), concentrated and purified by flash chromatography to provide the desired product (304.4 mg, 40%). MS calculated for C24H36F3N4O4: (M+H) 501.3; found 501.3.

Workup

  1. washwashed with saturated Na2CO3
  2. extractionThe aqueous layer was extracted with CH2Cl2 four times
  3. dry with materialThe combined organic layers were dried (MgSO4)
  4. concentrationconcentrated
  5. custompurified by flash chromatography

Sources & evidence

ORD record
ord-218ef053cda54d9984a1ee11cb053551
Source dataset
uspto-grants-2013_06
Patent number
US08470827B2

Reaction notes

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