Trifluoroacetic acid → HCID 178498771, compound

HRID 2404123Notes

Reaction equation

HRID 2404123 reaction equation
[C:1]([C@H:5]1[CH2:10][CH2:9][C@H:8]([O:11][C:12]2[C:13](C(F)(F)F)=[C:14]3[C:19](=[CH:20][CH:21]=2)[CH:18]=[C:17]([CH2:22][N:23]2[CH2:26][CH:25]([C:27]([O:29][CH3:30])=[O:28])[CH2:24]2)[CH:16]=[CH:15]3)[CH2:7][CH2:6]1)([CH3:4])([CH3:3])[CH3:2].C1C(=O)N([Cl:42])C(=O)C1.C(O)(C(F)(F)F)=O.C([O-])([O-])=O.[Na+].[Na+]>CC#N>[C:1]([C@H:5]1[CH2:10][CH2:9][C@H:8]([O:11][C:12]2[C:13]([Cl:42])=[C:14]3[C:19](=[CH:20][CH:21]=2)[CH:18]=[C:17]([CH2:22][N:23]2[CH2:26][CH:25]([C:27]([O:29][CH3:30])=[O:28])[CH2:24]2)[CH:16]=[CH:15]3)[CH2:7][CH2:6]1)([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 10340Sodium CarbonateHCID 31398ChlorosuccinimideHCID 178498770HCID 178498770, compound

Product 1

HCID 178498771HCID 178498771, compoundYield 43.1%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

Compound methyl 1-((6-(trans-4-tert-butylcyclohexyloxy)-5-(trifluoromethyl)naphthalen-2-yl)methyl)azetidine-3-carboxylate (140 mg, 0.34 mmol) and NCS (90 mg, 0.68 mmol, 2.0 eq.) were dissolved in MeCN (5 mL). Then CF3COOH (12 mg, 0.1 mmol, 0.3 eq.) was added to the mixture at 0° C. The mixture was warmed to r.t. and stirred for 1 h. Then the pH of the solution was adjusted to 7 with saturated Na2CO3, concentrated and the mixture was extracted by EtOAc. The organic layer was concentrated and purified by silica gel chromatography using PE/EA (6/1) to give product methyl 1-((6-((trans)-4-tert-butylcyclohexyloxy)-5-chloronaphthalen-2-yl)methyl)azetidine-3-carboxylate (65 mg, 43%) as a slight yellow oil. EDI-MS (M+1)+: 444.0. 1H NMR (400 MHz, CDCl3) δ 8.16 (d, 1H), 7.69-7.66 (m, 2H), 7.50-7.47 (m, 1H), 7.28-7.27 (m, 1H), 4.25-4.19 (m, 1H), 3.77 (s, 2H), 3.72 (s, 3H), 3.59-3.58 (m, 2H), 3.38-3.37 (m, 3H), 2.23-2.20 (m, 2H), 1.88-1.85 (m, 2H), 1.61-1.52 (m, 2H), 1.12-1.07 (m, 3H), 0.87 (s, 9H).

Workup

  1. concentrationconcentrated
  2. extractionthe mixture was extracted by EtOAc
  3. concentrationThe organic layer was concentrated
  4. custompurified by silica gel chromatography

Sources & evidence

ORD record
ord-b2e7c448574a46e2b2518d443f12dbe9
Source dataset
uspto-grants-2014_08
Patent number
US08802659B2

Reaction notes

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