Triethylamine → (1S,2S)-2-Phenyl-cyclopropanecarboxylic acid [(R)-2-hydroxy-1-(6-propoxy-pyridin-3-yl)-ethyl]-amide

HRID 1908682Notes

Reaction equation

HRID 1908682 reaction equation
C(N(CC)CC)C.[C:8]1([C@@H:14]2[CH2:16][C@H:15]2[C:17]([OH:19])=O)[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.[NH2:44][C@H:45]([C:48]1[CH:49]=[N:50][C:51]([O:54][CH2:55][CH2:56][CH3:57])=[CH:52][CH:53]=1)[CH2:46][OH:47]>CN(C=O)C.[Cl-].[Na+].O.CCOC(C)=O>[OH:47][CH2:46][C@H:45]([NH:44][C:17]([C@H:15]1[CH2:16][C@@H:14]1[C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1)=[O:19])[C:48]1[CH:49]=[N:50][C:51]([O:54][CH2:55][CH2:56][CH3:57])=[CH:52][CH:53]=1

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 237413trans-2-Phenylcyclopropanecarboxylic acidHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 86675616(R)-2-Amino-2-(6-propoxy-pyridin-3-yl)-ethanol

Product 1

HCID 71201933(1S,2S)-2-Phenyl-cyclopropanecarboxylic acid [(R)-2-hydroxy-1-(6-propoxy-pyridin-3-yl)-ethyl]-amideYield 29%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

Triethylamine (0.384 mL, 2.75 mmol) was added to a mixture of trans-2-phenyl-1-cyclopropanecarboxylic acid IM46 (223 mg, 1.38 mmol) and O-(benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (522 mg, 1.38 mmol) suspended in DMF (2 mL) in a small vial. The vial was vigorously agitated for 30 seconds and then left for 5 minutes. This mixture was added drop wise to (R)-2-Amino-2-(6-propoxy-pyridin-3-yl)-ethanol IM36 (270 mg, 1.4 mmol) dissolved in DMF (3 mL). After 1 h the mixture was poured into a mixture of EtOAc (40 mL) and brine (20 mL). The organic layer was dried over MgSO4 and evaporated to dryness. Flash chromatography (silica, 10-100% EtOAc in heptanes) gave the title compound as a white solid (0.134 g, 29%). LC-MS (m/z) 341.0 (MH+), tR=1.52 min (method A). 1H-NMR (600 MHz, DMSO) δ 8.53 (d, J=8.2 Hz, 1H), 8.04 (br s, 1H), 7.64-7.57 (m, 1H), 7.30-7.23 (m, 2H), 7.19-7.14 (m, 1H), 7.10 (d, J=7.3 Hz, 2H), 6.74 (d, J=8.5 Hz, 1H), 4.96-4.90 (m, 1H), 4.88-4.80 (m, 1H), 4.16 (t, J=6.7 Hz, 2H), 3.61-3.49 (m, 2H), 2.23-2.15 (m, 1H), 2.04-1.95 (m, 1H), 1.74-1.64 (m, 2H), 1.40-1.32 (m, 1H), 1.23-1.13 (m, 1H), 0.94 (t, J=7.4 Hz, 3H).

Workup

  1. waitleft for 5 minutes
  2. dry with materialThe organic layer was dried over MgSO4
  3. customevaporated to dryness

Sources & evidence

ORD record
ord-9c3fe631e67746478902ef2e31b24e34
Source dataset
uspto-grants-2013_12
Patent number
US08598213B2

Reaction notes

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