1,2-Dichloroethane → HCID 58780684, compound

HRID 1373659Notes

Reaction equation

HRID 1373659 reaction equation
[C:1]([N:5]1[CH2:10][CH2:9][C@@H:8]([C:11](O)=[O:12])[C@@H:7]([C:14]2[CH:19]=[CH:18][C:17]([F:20])=[CH:16][C:15]=2[F:21])[CH2:6]1)([CH3:4])([CH3:3])[CH3:2].C[N:23]1[CH2:28][CH2:27]O[CH2:25][CH2:24]1.[CH:29]1[CH:30]=[CH:31][C:32]2N(O)N=N[C:33]=2[CH:34]=1.[CH2:39](Cl)[CH2:40]Cl.[NH:43]1[CH2:48][CH2:47][NH:46][CH2:45][CH2:44]1.Cl>ClCCl>[C:1]([N:5]1[CH2:10][CH2:9][C@@H:8]([C:11]([N:43]2[CH2:48][CH2:47][N:46]([CH:25]([CH:33]3[CH2:32][CH2:31][CH2:30][CH2:29][CH2:34]3)[CH2:24][N:23]([CH2:39][CH3:40])[CH2:28][CH3:27])[CH2:45][CH2:44]2)=[O:12])[C@H:7]([C:14]2[CH:19]=[CH:18][C:17]([F:20])=[CH:16][C:15]=2[F:21])[CH2:6]1)([CH3:2])([CH3:4])[CH3:3]

Participants

8

Reactant 6

HCID 111,2-DichloroethaneHCID 313Hydrochloric AcidHCID 4837PiperazineHCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 86594666HCID 86594666, compound

Product 1

HCID 58780684HCID 58780684, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (3S,4R)-1-tert-butyl-3-(2,4-difluorophenyl)-piperidine-4-carboxylic acid A-4 (30 mg, 0.101 mmol) in dichloromethane (5 mL) was added 4-methylmorpholine (0.017 ml, 0.151 mmol), HOBt (15 mg, 0.111 mmol), EDC (29 mg, 0.1514 mmol), and piperazine K-2 (30.6 mg, 0.101 mmol). The reaction mixture was stirred at room temperature for 18 hours. The reaction mixture was then concentrated, purified by preparative TLC (10:1, CHCl3:2N NH3 in MeOH) to give a yellow oil, to which was added HCl (1.0 M in ether) and the resulting mixture was concentrated to give the title compound as a mixture of two diastereomers, D1 and D2. ESI-MS calc. for C32H52F2N4O: 546. Found: 547 (M+H). D1: NMR (500 MHz, CD3OD) 7.40–7.27 (m, 1H), 6.94–6.82 (m, 2H), 3.68–3.40 (m, 5H), 3.395–3.00 (m, 5H), 2.80–2.20 (m, 11H), 1.94–1.60 (m, 6H), 1.50–0.84 (m, 20H). D2: NMR (500 MHz, CD3OD) 7.40–7.27 (m, 1H), 6.94–6.82 (m, 2H), 3.68–3.00 (m, 10H), 2.80–2.2 (m, 11H), 2.00–1.60 (m, 6H), 1.40–0.80 (m, 20H).

Workup

  1. concentrationThe reaction mixture was then concentrated
  2. custompurified by preparative TLC (10:1, CHCl3:2N NH3 in MeOH)
  3. customto give a yellow oil
  4. concentrationthe resulting mixture was concentrated

Sources & evidence

ORD record
ord-ea8836d9a7334bbb800a10f26d50cdd0
Source dataset
uspto-grants-2007_01
Patent number
US07160886B2

Reaction notes

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