Hydrochloric Acid → (S)-2-({(3R,8S)-3-[4-(3,4-Dichloro-benzyloxy)-phenyl]-2,3,6,7,8,9-hexahydro-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl}-amino)-3-[4-(2,3-dimethyl-pyridin-4-yl)-phenyl]-propionic acid methyl ester

HRID 708633Notes

Reaction equation

HRID 708633 reaction equation
C(OC([N:8]1[C@H:17]([C:18](=[O:40])[NH:19][C@H:20]([C:36]([O:38][CH3:39])=[O:37])[CH2:21][C:22]2[CH:27]=[CH:26][C:25]([C:28]3[CH:33]=[CH:32][N:31]=[C:30]([CH3:34])[C:29]=3[CH3:35])=[CH:24][CH:23]=2)[CH2:16][C:15]2[CH:14]=[C:13]3[O:41][CH2:42][C@@H:43]([C:45]4[CH:50]=[CH:49][C:48]([O:51][CH2:52][C:53]5[CH:58]=[CH:57][C:56]([Cl:59])=[C:55]([Cl:60])[CH:54]=5)=[CH:47][CH:46]=4)[O:44][C:12]3=[CH:11][C:10]=2[CH2:9]1)=O)(C)(C)C.Cl>C(Cl)Cl>[CH3:39][O:38][C:36](=[O:37])[C@@H:20]([NH:19][C:18]([C@@H:17]1[CH2:16][C:15]2[CH:14]=[C:13]3[O:41][CH2:42][C@@H:43]([C:45]4[CH:50]=[CH:49][C:48]([O:51][CH2:52][C:53]5[CH:58]=[CH:57][C:56]([Cl:59])=[C:55]([Cl:60])[CH:54]=5)=[CH:47][CH:46]=4)[O:44][C:12]3=[CH:11][C:10]=2[CH2:9][NH:8]1)=[O:40])[CH2:21][C:22]1[CH:27]=[CH:26][C:25]([C:28]2[CH:33]=[CH:32][N:31]=[C:30]([CH3:34])[C:29]=2[CH3:35])=[CH:24][CH:23]=1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 58327244(3R,8S)-3-[4-(3,4-Dichloro-benzyloxy)-phenyl]-8-{(S)-2-[4-(2,3-dimethyl-pyridin-4-yl)-phenyl]-1-methoxycarbonyl-ethylcarbamoyl}-2,3,8,9-tetrahydro-6H-[1,4]dioxino[2,3-g]isoquinoline-7-carboxylic acid tert-butyl ester

Product 1

HCID 58327532(S)-2-({(3R,8S)-3-[4-(3,4-Dichloro-benzyloxy)-phenyl]-2,3,6,7,8,9-hexahydro-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl}-amino)-3-[4-(2,3-dimethyl-pyridin-4-yl)-phenyl]-propionic acid methyl esterYield 75.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

(3R,8S)-3-[4-(3,4-Dichloro-benzyloxy)-phenyl]-8-{(S)-2-[4-(2,3-dimethyl-pyridin-4-yl)-phenyl]-1-methoxycarbonyl-ethylcarbamoyl}-2,3,8,9-tetrahydro-6H-[1,4]dioxino[2,3-g]-isoquinoline-7-carboxylic acid tert-butyl ester (300 mg) was dissolved in 15 mL DCM and 7.5 mL 4N HCl (in dioxane) added. The reaction was stirred at room temperature for 2.5 hours, DCM was added and mixture was concentrated. The solid was suspended in EtOAc-THF (9:1) and washed with a 10% sodium carbonate solution. The organic layer was washed with brine, nd dried over sodium sulfate and concentrated. DCM added and the mixture concentrated to provide 0.2 g of the product. LCMS: m/z 753.

Workup

  1. concentrationmixture was concentrated
  2. washwashed with a 10% sodium carbonate solution
  3. washThe organic layer was washed with brine
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated
  6. additionDCM added
  7. concentrationthe mixture concentrated

Sources & evidence

ORD record
ord-91d614c821b54a8395c10c84a3f6653b
Source dataset
uspto-grants-2015_11
Patent number
US09175003B2

Reaction notes

Loading…