Hydrochloric Acid → 1-[4-(4-Cyclohexyl-3-trifluoromethyl-benzylsulfanyl)-benzyl]-azetidine-3-carboxylic acid

HRID 1828709Notes

Reaction equation

HRID 1828709 reaction equation
[CH:1]1([C:7]2[CH:26]=[CH:25][C:10]([CH2:11][S:12][C:13]3[CH:18]=[CH:17][C:16]([CH:19]4OCCCO4)=[CH:15][CH:14]=3)=[CH:9][C:8]=2[C:27]([F:30])([F:29])[F:28])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.Cl.[NH:32]1[CH2:35][CH:34]([C:36]([OH:38])=[O:37])[CH2:33]1.[BH3-]C#N.[Na+]>C1COCC1.C(OCC)C.C(N(CC)CC)C>[CH:1]1([C:7]2[CH:26]=[CH:25][C:10]([CH2:11][S:12][C:13]3[CH:14]=[CH:15][C:16]([CH2:19][N:32]4[CH2:35][CH:34]([C:36]([OH:38])=[O:37])[CH2:33]4)=[CH:17][CH:18]=3)=[CH:9][C:8]=2[C:27]([F:30])([F:28])[F:29])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 931923-azetidinecarboxylic AcidHCID 5003444Sodium cyanoborohydrideHCID 220577252-[4-(4-Cyclohexyl-3-trifluoromethyl-benzylsulfanyl)-phenyl]-[1,3]dioxane

Product 1

HCID 220577311-[4-(4-Cyclohexyl-3-trifluoromethyl-benzylsulfanyl)-benzyl]-azetidine-3-carboxylic acid

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolvent

Procedure

To a solution of 2-[4-(4-cyclohexyl-3-trifluoromethyl-benzylsulfanyl)-phenyl]-[1,3]dioxane (90 mg, 0.2 mmol) in THF (10 mL), is added aqueous HCl (2N, 0.7 mL). The solution is stirred at room temperature for 4 h. The solution is diluted with diethyl ether (30 mL), and washed with saturated aqueous NaHCO3 (3×10 mL). The organic layer is washed with saturated aqueous NaCl, dried over Na2SO4, and partially concentrated followed by dilution with MeOH (10 mL). To the resulting solution is added triethyl amine (0.5 mL) and azetidine-3-carboxylic acid (46 mmol, 0.4 mmol). The resulting mixture is stirred at 50° C. for 30 min. The reaction is cooled to room temperature and NaCNBH3 (63 mg, 1 mmol) is added. The resulting mixture is stirred for 30 min followed by concentration to dryness. The crude product is purified by preparative RP LC-MS to give 1-[4-(4-cyclohexyl-3-trifluoromethyl-benzylsulfanyl)-benzyl]-azetidine-3-carboxylic acid as a colorless oil. 1HNMR (400 MHz, CD3OD) δ7.55–7.54 (m, 2H), 7.52–7.35 (m, 5H), 4.39 (s, 2H), 4.35 (m, 4H), 4.17 (s, 2H), 3.68 (tt, 1H), 2.90 (tt, 1H), 1.87–1.75(m, 5H), 1.72–1.48 (m, 5H); MS (ES+): (464.2, M+1)+.

Workup

  1. washwashed with saturated aqueous NaHCO3 (3×10 mL)
  2. washThe organic layer is washed with saturated aqueous NaCl
  3. dry with materialdried over Na2SO4
  4. concentrationpartially concentrated
  5. stirringThe resulting mixture is stirred at 50° C. for 30 min
  6. temperatureThe reaction is cooled to room temperature
  7. stirringThe resulting mixture is stirred for 30 min
  8. concentrationfollowed by concentration to dryness
  9. customThe crude product is purified by preparative RP LC-MS

Sources & evidence

ORD record
ord-f11528336bec4c97926c8ba360548eda
Source dataset
uspto-grants-2006_06
Patent number
US07060697B2

Reaction notes

Loading…