Isopropyl chloroformate → HCID 24995278, compound

HRID 423700Notes

Reaction equation

HRID 423700 reaction equation
[F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].[CH3:8][C:9]1[CH:14]=[C:13]([S:15]([CH3:18])(=[O:17])=[O:16])[CH:12]=[CH:11][C:10]=1[C:19]1[CH:24]=[CH:23][C:22]([O:25][CH2:26][CH:27]2[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]2)=[CH:21][N:20]=1.Cl[C:34]([O:36][CH:37]([CH3:39])[CH3:38])=[O:35].C(N(CC)CC)C>C(Cl)Cl>[C:3]([OH:5])([C:2]([F:7])([F:6])[F:1])=[O:4].[C:34](=[O:35])([O-:16])[O-:36].[CH3:8][C:9]1[CH:14]=[C:13]([S:15]([CH3:18])(=[O:17])=[O:16])[CH:12]=[CH:11][C:10]=1[C:19]1[N:20]=[CH:21][C:22]([O:25][CH2:26][CH:27]2[CH2:32][CH2:31][N:30]([C:34]([O:36][CH:37]([CH3:39])[CH3:38])=[O:35])[CH2:29][CH2:28]2)=[CH:23][CH:24]=1

Participants

7

Reactant 3

HCID 7917Isopropyl chloroformateHCID 8471TriethylamineHCID 66673508HCID 66673508, compound

Product 3

HCID 6422Trifluoroacetic acidYield 0.05%HCID 19660Carbonate IonHCID 24995278HCID 24995278, compoundYield 68.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of 2-[2-methyl-4-(methylsulfonyl)phenyl]-5-[(4-piperidinylmethyl)oxy]pyridine trifluoroacetate (80 mg, 0.169 mmol), isopropyl chloroformate (1M in toluene, 0.169 mL, 0.169 mmol), and triethylamine (0.070 mL, 0.506 mmol) in CH2Cl2 (3 mL) was stirred at ambient temperature for 1 h, then concentrated. The crude product was purified by reverse-phase preparative HPLC using CH3CN:H2O gradient (5:95 to 90:10) with 0.05% TFA as a modifier, then free-based in CH2Cl2 with MP-Carbonate to give 26 mg (35%) of the title compound as a clear oil. 1H NMR (400 MHz, CDCl3): δ 8.38 (d, 1H, J=2.5 Hz), 7.86-7.76 (m, 2H), 7.55 (d, 1H, J=7.9 Hz), 7.37-7.31 (m, 1H), 7.29-7.25 (m, 1H), 4.92 (septet, 1H, J=6.2 Hz), 4.22 (bs, 2H), 3.90 (d, 2H, J=6.3 Hz), 3.05 (s, 3H), 2.90-2.70 (m, 2H), 2.43 (s, 3H), 2.09-1.95 (m, 1H), 1.95-1.80 (m, 2H), 1.39-1.22 (m, 8H); LRMS (ESI), m/z 447 (M+H).

Workup

  1. concentrationconcentrated
  2. customThe crude product was purified by reverse-phase preparative HPLC

Sources & evidence

ORD record
ord-9eb6251629364d13a60aa7db835a2fd2
Source dataset
uspto-grants-2012_01
Patent number
US08101634B2

Reaction notes

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