Triethylamine → (R)-2-[(4-Benzyloxy-1-methoxymethyl-7-phenoxy-isoquinoline-3-carbonyl)-amino]-propionic acid tert-butyl ester

HRID 1406103Notes

Reaction equation

HRID 1406103 reaction equation
[CH2:1]([O:8][C:9]1[C:18]2[C:13](=[CH:14][C:15]([O:19][C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)=[CH:16][CH:17]=2)[C:12]([CH2:26][O:27][CH3:28])=[N:11][C:10]=1[C:29](O)=[O:30])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CCN(CC)CC.ClC(OCC(C)C)=O.Cl.[C:48]([O:52][C:53](=[O:57])[C@@H:54]([CH3:56])[NH2:55])([CH3:51])([CH3:50])[CH3:49]>C(Cl)Cl>[C:48]([O:52][C:53](=[O:57])[C@H:54]([NH:55][C:29]([C:10]1[N:11]=[C:12]([CH2:26][O:27][CH3:28])[C:13]2[C:18]([C:9]=1[O:8][CH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)=[CH:17][CH:16]=[C:15]([O:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)[CH:14]=2)=[O:30])[CH3:56])([CH3:51])([CH3:50])[CH3:49]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 62365Isobutyl chloroformateHCID 16211919D-Alanine tert-butyl ester hydrochlorideHCID 667128304-Benzyloxy-1-methoxymethyl-7-phenoxy-isoquinoline-3-carboxylic acid

Product 1

HCID 66712878(R)-2-[(4-Benzyloxy-1-methoxymethyl-7-phenoxy-isoquinoline-3-carbonyl)-amino]-propionic acid tert-butyl esterYield 85.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a mixture of 4-Benzyloxy-1-methoxymethyl-7-phenoxy-isoquinoline-3-carboxylic acid (79 mg, 0.19 mmol), NEt3 (56 μl, 0.4 mmol), and CH2Cl2 (5 ml) cooled with an ice bath was added ClCO2iBu (26.5 μl, 0.2 mmol) with stirring. After stirring for 15 min (R)-alanine tert-butyl ester hydrochloride (36 mg, 0.2 mmol) was added and the mixture was allowed to warm up to ambient temperature overnight with stirring. Subsequently; the mixture was concentrated in vacuo. To the residue was added water (10 ml) and a few drops of aqueous 6N HCl. The mixture was extracted with EtOAc (2×15 ml). The organic phase was dried over MgSO4 and concentrated in vacuo. Purification by flash column chromatography on silica gel using EtOAc as the eluent gave the title compound as a tan oil (88 mg); MS-(+)-ion: M+23=565.2.

Workup

  1. temperaturecooled with an ice bath
  2. additionwas added
  3. stirringwith stirring
  4. concentrationthe mixture was concentrated in vacuo
  5. additionTo the residue was added water (10 ml) and a few drops of aqueous 6N HCl
  6. extractionThe mixture was extracted with EtOAc (2×15 ml)
  7. dry with materialThe organic phase was dried over MgSO4
  8. concentrationconcentrated in vacuo
  9. customPurification by flash column chromatography on silica gel

Sources & evidence

ORD record
ord-5b224790581545c6b63af8cf670cddc5
Source dataset
uspto-grants-2014_12
Patent number
US08916585B2

Reaction notes

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