Water → (2-{1-[2-(2,5-Dimethyl-phenyl)-acetyl]-piperidin-4-yl}-thiazol-4-yl)-carbamic acid tert-butyl ester

HRID 1042057Notes

Reaction equation

HRID 1042057 reaction equation
[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][C:3]=1[CH2:9][C:10]([N:12]1[CH2:17][CH2:16][CH:15]([C:18]2[S:19][CH:20]=[C:21](C(O)=O)[N:22]=2)[CH2:14][CH2:13]1)=[O:11].C([N:28]([CH2:31]C)CC)C.C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:40])C=CC=CC=1.O.[C:51]([OH:55])([CH3:54])([CH3:53])[CH3:52]>C(#N)C>[C:51]([O:55][C:31](=[O:40])[NH:28][C:21]1[N:22]=[C:18]([CH:15]2[CH2:14][CH2:13][N:12]([C:10](=[O:11])[CH2:9][C:3]3[CH:4]=[C:5]([CH3:8])[CH:6]=[CH:7][C:2]=3[CH3:1])[CH2:17][CH2:16]2)[S:19][CH:20]=1)([CH3:54])([CH3:53])[CH3:52]

Participants

7

Reactant 5

HCID 962WaterHCID 6386tert-ButanolHCID 8471TriethylamineHCID 199401P,P-Diphenylphosphinic azideHCID 66956465HCID 66956465, compound

Product 1

HCID 66957001(2-{1-[2-(2,5-Dimethyl-phenyl)-acetyl]-piperidin-4-yl}-thiazol-4-yl)-carbamic acid tert-butyl esterYield 73%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of 2-{1-[2-(2,5-dimethyl-phenyl)-acetyl]-piperidin-4-yl}-thiazole-4-carboxylic acid (5.65 g, 15.76 mmol) in tert-butanol (60 mL) is added triethylamine (5.2 mL, 36.2 mmol). After stirring 30 min. at RT, diphenylphosphoryl azide (6.9 mL, 31.5 mmol) is added and the reaction mixture is divided in 4 portions and each portion is irradiated under microwave (100° C., 15 min.). After cooling to RT, all portions are combined and water (1 mL) is added to the reaction mixture and stirred for 30 minutes. Acetonitrile (50 mL) is then added, followed by addition of basic Amberlyst A21. After stirring overnight at RT, the resin is filtered off, and solvents are evaporated under reduced pressure. The remainder is purified by column chromatography on silica gel (ethyl acetate/cyclohexane 7:3) to give (2-{1-[2-(2,5-dimethyl-phenyl)-acetyl]-piperidin-4-yl}-thiazol-4-yl)-carbamic acid tert-butyl ester (4.93 g, 73%). 1H-NMR (400 MHz, CDCl3): δ=1.53 (s, 9H), 1.53-1.61 (m, 1H), 1.67-1.79 (m, 1H), 1.95-2.04 (m, 1H), 2.08-2.14 (m, 1H), 2.25 (s, 3H), 2.30 (s, 3H), 2.80-2.90 (m, 1H), 3.06-3.20 (m, 2H), 3.68 (s, 2H), 3.80-3.89 (m, 1H), 4.68-4.74 (m, 1H), 6.95 (s, 1H), 6.98 (d, 1H), 7.07 (d, 1H), 7.23 (s, 1H). MS: m/z=430 (M+1).

Workup

  1. customeach portion is irradiated under microwave (100° C., 15 min.)
  2. temperatureAfter cooling to RT
  3. stirringstirred for 30 minutes
  4. additionfollowed by addition of basic Amberlyst A21
  5. stirringAfter stirring overnight at RT
  6. filtrationthe resin is filtered off
  7. customsolvents are evaporated under reduced pressure
  8. customThe remainder is purified by column chromatography on silica gel (ethyl acetate/cyclohexane 7:3)

Sources & evidence

ORD record
ord-cf72eadbfec84a4da692151e4376f55b
Source dataset
uspto-grants-2013_10
Patent number
US08557821B2

Reaction notes

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