Diisopropylethylamine → (S)-4-[(R)-5-(4-Methanesulfonyl-phenyl)-2,3-dihydro-furo[2,3-c]pyridin-2-yl]-piperidine-1-carboxylic acid 2,2,2-trifluoro-1-methyl-ethyl ester

HRID 872208Notes

Reaction equation

HRID 872208 reaction equation
[F:1][C:2]([F:19])([F:18])[C@@H:3]([O:5][C:6](=O)[O:7]C1C=CC([N+]([O-])=O)=CC=1)[CH3:4].[CH3:20][S:21]([C:24]1[CH:29]=[CH:28][C:27]([C:30]2[CH:31]=[C:32]3[CH2:38][C@H:37]([CH:39]4[CH2:44][CH2:43][NH:42][CH2:41][CH2:40]4)[O:36][C:33]3=[CH:34][N:35]=2)=[CH:26][CH:25]=1)(=[O:23])=[O:22].C(N(CC)C(C)C)(C)C>O1CCCC1>[F:1][C:2]([F:19])([F:18])[C@@H:3]([O:5][C:6]([N:42]1[CH2:43][CH2:44][CH:39]([C@@H:37]2[O:36][C:33]3=[CH:34][N:35]=[C:30]([C:27]4[CH:28]=[CH:29][C:24]([S:21]([CH3:20])(=[O:22])=[O:23])=[CH:25][CH:26]=4)[CH:31]=[C:32]3[CH2:38]2)[CH2:40][CH2:41]1)=[O:7])[CH3:4]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 687562104-nitrophenyl (2S)-1,1,1-trifluoropropan-2-yl carbonateHCID 71208609(R)-5-(4-methanesulfonyl-phenyl)-2-piperidin-4-yl-2,3-dihydro-furo[2,3-c]pyridine

Product 1

HCID 90050905(S)-4-[(R)-5-(4-Methanesulfonyl-phenyl)-2,3-dihydro-furo[2,3-c]pyridin-2-yl]-piperidine-1-carboxylic acid 2,2,2-trifluoro-1-methyl-ethyl ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Carbonic acid 4-nitro-phenyl ester (S)-2,2,2-trifluoro-1-methyl-ethyl ester (85 mg) is added to a solution of (R)-5-(4-methanesulfonyl-phenyl)-2-piperidin-4-yl-2,3-dihydro-furo[2,3-c]pyridine (100 mg) and N,N-diisopropyl-ethylamine (60 μL) in tetrahydrofuran (2 mL) at room temperature. The solution is stirred at room temperature overnight and then washed with 1 N aqueous NaOH solution (3×), water, and brine. The organic phase is dried (MgSO4) and concentrated. The residue is chromatographed on silica gel (cyclohexane/ethyl acetate 1:1→1:3) to give the title compound. LC (method 1): tR=1.00 min; Mass spectrum (ESI+): m/z=499 [M+H]+.

Workup

  1. washwashed with 1 N aqueous NaOH solution (3×), water, and brine
  2. dry with materialThe organic phase is dried (MgSO4)
  3. concentrationconcentrated
  4. customThe residue is chromatographed on silica gel (cyclohexane/ethyl acetate 1:1→1:3)

Sources & evidence

ORD record
ord-d090cc97d7564197b7a4285f352a4de1
Source dataset
uspto-grants-2015_03
Patent number
US08975277B2

Reaction notes

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