Acetic Acid → 1-[6-(4-tert-Butyl-cyclohexyloxy)-naphthalen-2-ylmethyl]-4-ethyl-piperidine-4-carboxylic acid

HRID 525452Notes

Reaction equation

HRID 525452 reaction equation
[CH2:1]([C:3]1([C:9]([OH:11])=[O:10])[CH2:8][CH2:7][NH:6][CH2:5][CH2:4]1)[CH3:2].[C:12]([CH:16]1[CH2:21][CH2:20][CH:19]([O:22][C:23]2[CH:24]=[C:25]3[C:30](=[CH:31][CH:32]=2)[CH:29]=[C:28]([CH:33]=O)[CH:27]=[CH:26]3)[CH2:18][CH2:17]1)([CH3:15])([CH3:14])[CH3:13].C(O)(=O)C.CO.C([BH3-])#N.[Na+]>>[C:12]([CH:16]1[CH2:21][CH2:20][CH:19]([O:22][C:23]2[CH:24]=[C:25]3[C:30](=[CH:31][CH:32]=2)[CH:29]=[C:28]([CH2:33][N:6]2[CH2:5][CH2:4][C:3]([CH2:1][CH3:2])([C:9]([OH:11])=[O:10])[CH2:8][CH2:7]2)[CH:27]=[CH:26]3)[CH2:18][CH2:17]1)([CH3:15])([CH3:14])[CH3:13]

Participants

6

Reactant 5

HCID 176Acetic AcidHCID 887MethanolHCID 5003444Sodium cyanoborohydrideHCID 509442034-Ethylpiperidine-4-carboxylic acidHCID 866684126-(trans-4-Tert-butylcyclohexyloxy)-2-naphthaldehyde

Product 1

HCID 601628281-[6-(4-tert-Butyl-cyclohexyloxy)-naphthalen-2-ylmethyl]-4-ethyl-piperidine-4-carboxylic acidYield 2%

Procedure

4-ethylpiperidine-4-carboxylic acid (0.184 g, 1.17 mmol) was combined with 6-(4-tert-Butyl-cyclohexyloxy)-naphthalene-2-carbaldehyde (0.3 g, 0.9 mmol), Acetic acid (0.19 mL, 3.4 mmol) in Methanol (1.9 mL, 48 mmol) and stirred for 30 min. The reaction was then cooled to 0° C. on an icebath and sodium cyanoborohydride (90.9 mg, 1.4 mmol) was added. The reaction was then allowed to warm to room temperature while stirring overnight. Reaction was then concentrated to about 4-5 mL then purified directly via reverse phase chromatography (5-95% CH3CN/Water (0.1% TFA), C18, 150 mm). The product was then lyophilized to dryness to give 7 mg 1-[6-(4-tert-Butyl-cyclohexyloxy)-naphthalen-2-ylmethyl]-4-ethyl-piperidine-4-carboxylic acid as a white solid (2%). ESI-MS: 452 (M+1)+. 1H NMR (DMSO-d6, 400 MHz): δ (ppm) 7.75-8.00 (m, 3H), 7.47-7.61 (m, 1H), 7.43 (s, 1H), 7.07-7.28 (m, 1H), 4.44 (m, 3H), 3.29-3.54 (m, 2H), 2.74-3.03 (m, 2H), 2.20 (s, 3H), 1.64-1.98 (m, 3H), 1.02-1.65 (m, 9H), 0.89 (s, 9H), 0.76-0.83 (m, 3H).

Workup

  1. additionwas added
  2. stirringwhile stirring overnight
  3. customReaction
  4. concentrationwas then concentrated to about 4-5 mL
  5. customthen purified directly via reverse phase chromatography (5-95% CH3CN/Water (0.1% TFA), C18, 150 mm)

Sources & evidence

ORD record
ord-641f86919b3846df86baf029209c9ebb
Source dataset
uspto-grants-2016_05
Patent number
US09340527B2

Reaction notes

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