Triethylamine → (2R)-N-[(2S)-2-hydroxy-3-phenoxypropyl]-6-iodo-3,4-dihydro-2H-chromene-2-carboxamide

HRID 47678Notes

Reaction equation

HRID 47678 reaction equation
[NH2:1][CH2:2][C@H:3]([OH:12])[CH2:4][O:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.[I:13][C:14]1[CH:15]=[C:16]2[C:21](=[CH:22][CH:23]=1)[O:20][C@@H:19]([C:24](O)=[O:25])[CH2:18][CH2:17]2.Cl.CN(C)CCCN=C=NCC.O.ON1C2C=CC=CC=2N=N1.C(N(CC)CC)C>C(Cl)Cl.O>[OH:12][C@H:3]([CH2:4][O:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)[CH2:2][NH:1][C:24]([C@H:19]1[CH2:18][CH2:17][C:16]2[C:21](=[CH:22][CH:23]=[C:14]([I:13])[CH:15]=2)[O:20]1)=[O:25]

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 1133101(2S)-(-)-1-Amino-3-phenoxy-2-propanolHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 9966213(2R)-6-Iodochromane-2-carboxylic acid

Product 1

HCID 10161252(2R)-N-[(2S)-2-hydroxy-3-phenoxypropyl]-6-iodo-3,4-dihydro-2H-chromene-2-carboxamideYield 77%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

A solution containing (2S)-1-amino-3-phenoxy-2-propanol (Example 53, 11.97 mmol, 1.0 eq.), (2R)-6-iodo-3,4-dihydro-2H-chromene-2-carboxylic acid (Example 7, 11.97 mmol, 1.0 eq.), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (23.98 mmol, 2.0 eq.), 1-hydroxybenzotriazole hydrate (23.94 mmol, 2.0 eq.), and triethylamine (23.94 mmol, 2.0 eq.) in CH2Cl2 (200 mL) was stirred at room temperature for 3 hours. To the resulting solution was added water and two-phase mixture was extracted with CH2Cl2. The organic extracts were washed with water and brine, dried over anhydrous sodium sulfate, concentrated and purified by medium pressure column chromatography (Biotage 40S normal phase silica gel column, hexanes:EtOAc=2:1). The product was obtained as a white solid in 77% yield. MH+=454.1, retention time (LC-MS)=3.03 min.

Workup

  1. extractionwas extracted with CH2Cl2
  2. washThe organic extracts were washed with water and brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. concentrationconcentrated
  5. custompurified by medium pressure column chromatography (Biotage 40S normal phase silica gel column, hexanes:EtOAc=2:1)
  6. customThe product was obtained as a white solid in 77% yield

Sources & evidence

ORD record
ord-9653f0322f2f4a4ba7b0eb417b484daa
Source dataset
uspto-grants-2004_03
Patent number
US06699860B2

Reaction notes

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