Diisopropylethylamine → HCID 67025902, compound

HRID 1951152Notes

Reaction equation

HRID 1951152 reaction equation
[F:1][C:2]([F:9])([F:8])[CH2:3][CH2:4][C:5](O)=[O:6].F[B-](F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C.[Cl:41][C:42]1[CH:43]=[C:44]([CH:49]2[CH:53]([NH:54][CH3:55])[CH2:52][N:51]([C:56]([CH:58]3[CH2:63][CH2:62][N:61]([C:64]([C:66]4([CH3:69])[CH2:68][CH2:67]4)=[O:65])[CH2:60][CH2:59]3)=[O:57])[CH2:50]2)[CH:45]=[CH:46][C:47]=1[Cl:48]>CN1C(=O)CCC1.C(OCC)(=O)C>[Cl:41][C:42]1[CH:43]=[C:44]([CH:49]2[CH2:50][N:51]([C:56]([CH:58]3[CH2:59][CH2:60][N:61]([C:64]([C:66]4([CH3:69])[CH2:67][CH2:68]4)=[O:65])[CH2:62][CH2:63]3)=[O:57])[CH2:52][CH:53]2[N:54]([CH3:55])[C:5](=[O:6])[CH2:4][CH2:3][C:2]([F:9])([F:8])[F:1])[CH:45]=[CH:46][C:47]=1[Cl:48]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 27770854,4,4-Trifluorobutanoic acidHCID 67025815[(3SR,4RS)-3-(3,4-Dichloro-phenyl)-4-methylamino-pyrrolidin-1-yl]-[1-(1-methyl-cyclopropanecarbonyl)-piperidin-4-yl]-methanone

Product 1

HCID 67025902HCID 67025902, compoundYield 77%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 13387N-methyl-2-pyrrolidoneSolvent2×

Procedure

To a solution of 4,4,4-trifluorobutyric acid (43 mg, 0.304 mmol) in NMP (1 ml) was added at ambient temperature 2-(1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium tetrafluoroborate (89 mg, 0.28 mmol) and N,N-diisopropyl ethyl amine (130 μl, 0.760 mmol). After stirring for 15 min a solution {4-[(3SR,4RS)-3-(3,4-dichloro-phenyl)-4-methylamino-pyrrolidine-1-carbonyl]-piperidin-1-yl}-(1-methyl-cyclopropyl)-methanone (111 mg, 0.253 mmol) in NMP (1 mL) was added and stirred for 18 h at ambient temperature. The reaction mixture was diluted with ethyl acetate (15 mL) and washed with aqueous sodium carbonate (1 M, 15 mL), water (15 mL) and brine (15 mL). The aqueous layers were extracted with ethyl acetate (15 mL) and the combined organic layers were dried over sodium sulfate. Purification by chromatography (SiO2, heptane:ethyl acetate:methanol=20:80:0 to 0:85:15) afforded the title compound (109 mg, 77%) as an off-white foam. MS m/e: 562.2 [M]+.

Workup

  1. additionwas added
  2. washwashed with aqueous sodium carbonate (1 M, 15 mL), water (15 mL) and brine (15 mL)
  3. extractionThe aqueous layers were extracted with ethyl acetate (15 mL)
  4. dry with materialthe combined organic layers were dried over sodium sulfate
  5. customPurification by chromatography (SiO2, heptane:ethyl acetate:methanol=20:80:0 to 0:85:15)

Sources & evidence

ORD record
ord-b06c6d8d5d4b454f9c5c4de5c8ec2ec8
Source dataset
uspto-grants-2013_03
Patent number
US08404679B2

Reaction notes

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