Triphenylphosphine → (1S,2S)-2-(4-{(R)-7-Fluoro-4-[4-(2-morpholin-4-yl-ethoxy)-phenoxy]-indan-1-yloxy}-phenyl)-cyclopropanecarboxylic acid ethyl ester

HRID 625692Notes

Reaction equation

HRID 625692 reaction equation
[CH2:1]([O:3][C:4]([C@H:6]1[CH2:8][C@@H:7]1[C:9]1[CH:14]=[CH:13][C:12]([O:15][C@H:16]2[C:24]3[C:19](=[C:20]([O:26][C:27]4[CH:32]=[CH:31][C:30]([OH:33])=[CH:29][CH:28]=4)[CH:21]=[CH:22][C:23]=3[F:25])[CH2:18][CH2:17]2)=[CH:11][CH:10]=1)=[O:5])[CH3:2].O[CH2:35][CH2:36][N:37]1[CH2:42][CH2:41][O:40][CH2:39][CH2:38]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)(C)C)=O)=NC(OC(C)(C)C)=O>O1CCCC1>[CH2:1]([O:3][C:4]([C@H:6]1[CH2:8][C@@H:7]1[C:9]1[CH:10]=[CH:11][C:12]([O:15][C@H:16]2[C:24]3[C:19](=[C:20]([O:26][C:27]4[CH:32]=[CH:31][C:30]([O:33][CH2:35][CH2:36][N:37]5[CH2:42][CH2:41][O:40][CH2:39][CH2:38]5)=[CH:29][CH:28]=4)[CH:21]=[CH:22][C:23]=3[F:25])[CH2:18][CH2:17]2)=[CH:13][CH:14]=1)=[O:5])[CH3:2]

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 611632-MorpholinoethanolHCID 97268Di-tert-butyl azodicarboxylateHCID 118093735(1S,2S)-2-{4-[(R)-7-Fluoro-4-(4-hydroxy-phenoxy)-indan-1-yloxy]-phenyl}-cyclopropanecarboxylic acid ethyl ester2×

Product 1

HCID 118093751(1S,2S)-2-(4-{(R)-7-Fluoro-4-[4-(2-morpholin-4-yl-ethoxy)-phenoxy]-indan-1-yloxy}-phenyl)-cyclopropanecarboxylic acid ethyl ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

(1S,2S)-2-{4-[(R)-7-Fluoro-4-(4-hydroxy-phenoxy)-indan-1-yloxy]-phenyl}-cyclopropanecarboxylic acid ethyl ester (Intermediate 7, 140 mg, 0.29 mmol), N-(2-hydroxyethyl)morpholine (42 mg, 0.32 mmol), and triphenylphosphine (84 mg, 0.32 mmol) are suspended in dry tetrahydrofuran (5 mL) and cooled to 0° C. Di-tert-butyl azodicarboxylate (74 mg, 0.32 mmol) is added, the mixture is stirred for 2 hours at 0° C. then 2 h at room temperature. The solvent is removed under vacuum and residue is purified by flash chromatography (0-20% ethyl acetate in cyclohexane) to give the title compound. (Yield 175 mg, 55% content). LC (METHOD 6): tR=0.57 min; Mass spectrum (ES+): m/z=562 [M+H]+.

Workup

  1. custom2 h
  2. customat room temperature
  3. customThe solvent is removed under vacuum and residue
  4. customis purified by flash chromatography (0-20% ethyl acetate in cyclohexane)

Sources & evidence

ORD record
ord-9b8d4a1bd48c4d91a50deba0434b3e3d
Source dataset
uspto-grants-2016_04
Patent number
US09308194B2

Reaction notes

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