Diisopropylethylamine → HCID 69900480, compound

HRID 2308091Notes

Reaction equation

HRID 2308091 reaction equation
[Li+].[Cl:2][C:3]1[CH:8]=[CH:7][N:6]=[C:5]2[CH:9]=[C:10]([C:12]([O-:14])=O)[S:11][C:4]=12.Cl.[CH3:16][O:17][C:18]([C@@H:20]1[CH2:24][C@@H:23]([OH:25])[CH2:22][NH:21]1)=[O:19].C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C.CCOC(C)=O>[CH3:16][O:17][C:18]([C@@H:20]1[CH2:24][C@@H:23]([OH:25])[CH2:22][N:21]1[C:12]([C:10]1[S:11][C:4]2[C:5](=[N:6][CH:7]=[CH:8][C:3]=2[Cl:2])[CH:9]=1)=[O:14])=[O:19]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 114353194-Hydroxy-L-proline methyl ester hydrochlorideHCID 23677819Lithium 7-chlorothieno[3,2-b]pyridine-2-carboxylate

Product 1

HCID 69900480HCID 69900480, compoundYield 70%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

In 10 mL of DMF was added 3.0 g (16.7 mmol) of 7-Chloro-thieno[3,2-b]pyridine-2-carboxylic acid lithium salt, 3.20 g (14.66 mmol) of (2S,4R)-4-Hydroxy-pyrrolidine-2-carboxylic acid methyl ester hydrochloride, PyBop (9.12 g (17.5 mmol) and 5.59 mL (32.1 mmol) of DIEA and the mixture was stirred for 24 h. To the mixture was added 50 mL of EtOAc was washed with 50/50 aq. NaHCO3 (2×50 mL). The organic layer was dried over Na2SO4 and concentrated to give an amber oil. Purification through 100 mL of silica eluting with EtOAc:CH2Cl2 (1:1) gave crude product. Diethyl ethyl was used to triturate (2×5 mL) the residue to afford 3.43 g (70%) of (2S,4R)-1-(7-Chloro-thieno[3,2-b]pyridine-2-carbonyl)-4-hydroxy-pyrrolidine-2-carboxylic acid methyl ester as off-white solid. HPLC: Rt 3.36 min. (98.2% area). LCMS (ESI) (M+H+) m/z: 341.0.

Workup

  1. washwas washed with 50/50 aq. NaHCO3 (2×50 mL)
  2. dry with materialThe organic layer was dried over Na2SO4
  3. concentrationconcentrated
  4. customto give an amber oil
  5. customPurification through 100 mL of silica eluting with EtOAc:CH2Cl2 (1:1)
  6. customgave crude product
  7. customto triturate (2×5 mL) the residue

Sources & evidence

ORD record
ord-52a1dd47902f42a1b0a66882e2e00e1e
Source dataset
uspto-grants-2004_12
Patent number
US06833456B2

Reaction notes

Loading…