3-(Methylthio)-1-propanol → HCID 118093707, compound

HRID 625693Notes

Reaction equation

HRID 625693 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])=[C:29]([F:34])[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].[CH3:35]SCCCO.[C:41]1(P(C2C=CC=CC=2)C2C=CC=CC=2)[CH:46]=CC=C[CH:42]=1.N(C(OC(C)(C)C)=O)=NC(OC(C)(C)C)=O.O[O:77][S:78]([O-:80])=O.[K+]>O1CCCC1.C(OCC)(=O)C.O>[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][CH2:42][CH2:41][CH2:46][S:78]([CH3:35])(=[O:80])=[O:77])=[C:29]([F:34])[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

9

Reactant 5

HCID 104483-(Methylthio)-1-propanol2×HCID 11776TriphenylphosphineHCID 97268Di-tert-butyl azodicarboxylate2×HCID 23707502Potassium hydroxy sulfiteHCID 118093744HCID 118093744, compound2×

Product 1

HCID 118093707HCID 118093707, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

(1S,2S)-2-{4-[(R)-7-Fluoro-4-(3-fluoro-4-hydroxy-phenoxy)-indan-1-yloxy]-phenyl}-cyclopropanecarboxylic acid ethyl ester (Intermediate 9, 200 mg, 0.43 mmol), 3-methylthiopropanol (0.044 mL, 0.43 mmol), triphenylphosphine (120 mg, 0.47 mmol) and di-tert-butyl azodicarboxylate (110 mg, 0.47 mmol) are suspended in dry tetrahydrofuran (5 mL) and stirred overnight. A further quantity of 3-methylthiopropanol (0.044 mL, 0.43 mmol), and di-tert-butyl azodicarboxylate (110 mg, 0.47 mmol) are added and the mixture stirred for a further 24 hours. The solvent is removed under vacuum and the residue is purified by flash chromatography (gradient of ethyl acetate in cyclohexane) to give a residue which is suspended in a 1:1 mixture of tetrahydrofuran and water (4 mL) and oxone is added (380 mg, 0.62 mmol). The mixture is stirred for 2 hours then diluted with ethyl acetate and washed with water. The solvent is removed and the residue is purified by flash chromatography (0-50% ethyl acetate in cyclohexane) to give the title compound. (Yield 50 mg). LC (METHOD 5): tR=1.47 min; Mass spectrum (ES+): m/z=587 [M+H]+.

Workup

  1. stirringthe mixture stirred for a further 24 hours
  2. customThe solvent is removed under vacuum
  3. customthe residue is purified by flash chromatography (gradient of ethyl acetate in cyclohexane)
  4. customto give a residue which
  5. additionis added (380 mg, 0.62 mmol)
  6. stirringThe mixture is stirred for 2 hours
  7. washwashed with water
  8. customThe solvent is removed
  9. customthe residue is purified by flash chromatography (0-50% ethyl acetate in cyclohexane)

Sources & evidence

ORD record
ord-7dab52df7df04ece97be3d39f3d04ce7
Source dataset
uspto-grants-2016_04
Patent number
US09308194B2

Reaction notes

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