Hydrochloric Acid → 4-[4-(4-Methanesulfonyl-phenoxymethyl)-thiazol-2-yl]-piperidine-1-carboxylic acid isopropyl ester

HRID 1869461Notes

Reaction equation

HRID 1869461 reaction equation
Cl.[CH3:2][S:3]([C:6]1[CH:24]=[CH:23][C:9]([O:10][CH2:11][C:12]2[N:13]=[C:14]([CH:17]3[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]3)[S:15][CH:16]=2)=[CH:8][CH:7]=1)(=[O:5])=[O:4].C1COCC1.Cl[C:31]([O:33][CH:34]([CH3:36])[CH3:35])=[O:32]>CCN(CC)CC>[CH:34]([O:33][C:31]([N:20]1[CH2:21][CH2:22][CH:17]([C:14]2[S:15][CH:16]=[C:12]([CH2:11][O:10][C:9]3[CH:8]=[CH:7][C:6]([S:3]([CH3:2])(=[O:4])=[O:5])=[CH:24][CH:23]=3)[N:13]=2)[CH2:18][CH2:19]1)=[O:32])([CH3:36])[CH3:35]

Participants

6

Reactant 4

HCID 313Hydrochloric Acid2×HCID 7917Isopropyl chloroformateHCID 8028TetrahydrofuranHCID 579868424-[4-(4-Methanesulfonyl-phenoxymethyl)-thiazol-2-yl]-piperidine

Product 1

HCID 250247204-[4-(4-Methanesulfonyl-phenoxymethyl)-thiazol-2-yl]-piperidine-1-carboxylic acid isopropyl ester

Reagents, catalysts & solvents 1

HCID 8471TriethylamineSolvent

Procedure

To the HCl salt (Intermediate 3, 43 mg, ˜0.12 mmol) of 4-[4-(4-Methanesulfonyl-phenoxymethyl)-thiazol-2-yl]-piperidine was added 3 mL of THF, followed by isopropyl chloroformate (1.0 M solution in toluene, 0.15 mL, 0.15 mmol) and Et3N (0.05 mL). The resulting mixture was stirred at room temperature for 2 hours, and then partitioned between EtOAc and H2O. After concentration of the organic layer in vacuo, the residue was purified by silica gel column chromatography with EtOAc/hexanes (40-70%) to give the desired product. 1H NMR (CDCl3): δ 7.86 (2H, d, J=9.0 Hz), 7.23 (1H, s), 7.11 (2H, d, J=9.0 Hz), 5.22 (2H, s), 4.92 (1H, m), 4.24 (2H, m), 3.17 (1H, m), 3.03 (3H, s), 2.90 (2H, m), 2.10 (2H, m), 1.72 (2H, m), 1.23 (6H, d, J=6.4 Hz).

Workup

  1. custompartitioned between EtOAc and H2O
  2. customAfter concentration of the organic layer in vacuo, the residue was purified by silica gel column chromatography with EtOAc/hexanes (40-70%)

Sources & evidence

ORD record
ord-fe88402a1f4541d0a736d107449d257d
Source dataset
uspto-grants-2009_12
Patent number
US07638541B2

Reaction notes

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