Trifluoroacetic acid → N-(2-hydroxy-2-methylpropyl)-N-[(2,4-dichloro-1,3-thiazol-5-yl)methyl]piperidin-4-amine

HRID 2111937Notes

Reaction equation

HRID 2111937 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][CH:11]([N:14]([CH2:20][C:21]2[S:25][C:24]([Cl:26])=[N:23][C:22]=2[Cl:27])[CH2:15][C:16]([OH:19])([CH3:18])[CH3:17])[CH2:10][CH2:9]1)=O)(C)(C)C.C1(OC)C=CC=CC=1.FC(F)(F)C(O)=O>ClCCl>[OH:19][C:16]([CH3:18])([CH3:17])[CH2:15][N:14]([CH2:20][C:21]1[S:25][C:24]([Cl:26])=[N:23][C:22]=1[Cl:27])[CH:11]1[CH2:10][CH2:9][NH:8][CH2:13][CH2:12]1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 7519AnisoleHCID 685774114-{[(2,4-Dichloro-thiazol-5-yl)methyl]-(2-hydroxy-2-methyl-propyl)-amino}-piperidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 57640324N-(2-hydroxy-2-methylpropyl)-N-[(2,4-dichloro-1,3-thiazol-5-yl)methyl]piperidin-4-amineYield 99.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Add 4-{[(2,4-dichloro-thiazol-5-yl)methyl]-(2-hydroxy-2-methyl-propyl)-amino}-piperidine-1-carboxylic acid tert-butyl ester (0.4487 g, 1.02 mmol) to a stirred solution of dichloromethane (60 mL) and anisole (9.0 mL, 82.8 mmol). Cool the reaction to 0° C. Add the trifluoroacetic acid (6.0 mL, 72.9 mmol). Stir the reaction for 10 minutes at 0° C. and then for 2 hours at room temperature. The reaction is loaded directly onto a 10 g prepacked SCX-2 cartridge and washed with methanol (200 mL). The product is then eluted off with 2M ammonia in methanol (100 mL) and concentrated on a rotary evaporator to yield 0.3448 g (99%) of N-(2-hydroxy-2-methylpropyl)-N-[(2,4-dichloro-1,3-thiazol-5-yl)methyl]piperidin-4-amine: mass spectrum (ion spray): m/z=338.1 (M+1); 1H NMR (CDCl3): δ=3.97 (s, 2H), 3.18-3.15 (m, 2H), 2.59-2.53 (m, 5H), 1.80-1.70 (m, 4H), 1.49-1.39 (m, 2H), 1.22 (s, 6H).

Workup

  1. temperatureCool
  2. customthe reaction to 0° C
  3. customthe reaction for 10 minutes at 0° C.
  4. washwashed with methanol (200 mL)
  5. washThe product is then eluted off with 2M ammonia in methanol (100 mL)
  6. concentrationconcentrated on a rotary evaporator

Sources & evidence

ORD record
ord-17bb1db4678f444fa749082396809c30
Source dataset
uspto-grants-2009_04
Patent number
US07521462B2

Reaction notes

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