Hydrochloric Acid → (3R,4R)-4-[4-[3-(2-methoxy-benzyloxy)-propoxy]-phenyl]-3-[1-(2-ureido-ethyl)-1,2,3,4-tetrahydro-quinolin-7-ylmethoxy]-piperidine-1-carboxylic acid tert-butyl ester

HRID 1531518Notes

Reaction equation

HRID 1531518 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C@H:11]([C:14]2[CH:19]=[CH:18][C:17]([O:20][CH2:21][CH2:22][CH2:23][O:24][CH2:25][C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=3[O:32][CH3:33])=[CH:16][CH:15]=2)[C@@H:10]([O:34][CH2:35][C:36]2[CH:45]=[C:44]3[C:39]([CH2:40][CH2:41][CH2:42][N:43]3[CH2:46][CH2:47][NH2:48])=[CH:38][CH:37]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[O-:49][C:50]#[N:51].[Na+].Cl.C(=O)(O)[O-].[Na+]>O1CCCC1.O>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C@H:11]([C:14]2[CH:19]=[CH:18][C:17]([O:20][CH2:21][CH2:22][CH2:23][O:24][CH2:25][C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=3[O:32][CH3:33])=[CH:16][CH:15]=2)[C@@H:10]([O:34][CH2:35][C:36]2[CH:45]=[C:44]3[C:39]([CH2:40][CH2:41][CH2:42][N:43]3[CH2:46][CH2:47][NH:48][C:50]([NH2:51])=[O:49])=[CH:38][CH:37]=2)[CH2:9]1)=[O:7])([CH3:3])([CH3:2])[CH3:4]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 516892Sodium BicarbonateHCID 517096Sodium CyanateHCID 69486181(3R,4R)-3-[1-(2-amino-ethyl)-1,2,3,4-tetrahydro-quinolin-7-ylmethoxy]-4-[4-[3-(2-methoxy-benzyloxy)-propoxy]-phenyl]-piperidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 69489118(3R,4R)-4-[4-[3-(2-methoxy-benzyloxy)-propoxy]-phenyl]-3-[1-(2-ureido-ethyl)-1,2,3,4-tetrahydro-quinolin-7-ylmethoxy]-piperidine-1-carboxylic acid tert-butyl esterYield 85.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 0.103 g (0.156 mmol) (3R,4R)-3-[1-(2-amino-ethyl)-1,2,3,4-tetrahydro -quinolin-7-ylmethoxy]-4-[4-[3-(2-methoxy-benzyloxy)-propoxy]-phenyl]-piperidine-1-carboxylic acid tert-butyl ester [example 15(b)] in 2 ml of tetrahydrofuran was added a solution of 0.101 g (1.56 mmol, 10.0 equiv.) of sodium cyanate in 1 ml of water. The resulting suspension was cooled to 0° C. and 0.156 ml (0.156 mmol, 1.0 equiv.) of 1 N HCl solution was added dropwise. The reaction flask was stoppered and the suspension was stirred for 2 h at 25° C. The reaction mixture was poured into 50 ml of an ice/water mixture, the pH was adjusted to 8 by addition of saturated sodium bicarbonate solution, and the aqueous phase was extracted three times with 50 ml of ethyl acetate. The combined organic phases were washed twice with 25 ml of water, evaporated under reduced pressure and dried in a high vacuum. The thus obtained crude product was purified by chromatography on silica gel using a 100:10:1 v/v/v mixture of dichloromethane/methanol/28% ammonium hydroxide solution as eluent to yield 0.106 g (0.133 mmol, 85.3% of theory) of (3R,4R)-4-[4-[3-(2-methoxy-benzyloxy)-propoxy]-phenyl]-3-[1-(2-ureido-ethyl)-1,2,3,4-tetrahydro-quinolin-7-ylmethoxy]-piperidine-1-carboxylic acid tert-butyl ester as a yellow oil; MS: 799 (M+H)+.

Workup

  1. extractionthe aqueous phase was extracted three times with 50 ml of ethyl acetate
  2. washThe combined organic phases were washed twice with 25 ml of water
  3. customevaporated under reduced pressure
  4. customdried in a high vacuum
  5. customThe thus obtained crude product
  6. customwas purified by chromatography on silica gel using
  7. additiona 100:10:1 v/v/v mixture of dichloromethane/methanol/28% ammonium hydroxide solution as eluent

Sources & evidence

ORD record
ord-7e0402f8fedb480c9e5264204d6db098
Source dataset
uspto-grants-2001_03
Patent number
US06197959B1

Reaction notes

Loading…