Triethylamine → HCID 67006489, compound

HRID 564347Notes

Reaction equation

HRID 564347 reaction equation
[C:1]([Si:5]([CH3:36])([CH3:35])[O:6][CH:7]([CH2:11][CH2:12][CH:13]1[CH:22]([S:23]([C:26]2[CH:31]=[CH:30][C:29]([Cl:32])=[CH:28][CH:27]=2)(=[O:25])=[O:24])[C:21]2[C:16](=[C:17]([F:34])[CH:18]=[CH:19][C:20]=2[F:33])[O:15][CH2:14]1)[CH2:8][CH2:9]O)([CH3:4])([CH3:3])[CH3:2].CCN(CC)CC.CS(Cl)(=O)=O.CC([O-])(C)C.[K+]>C(Cl)Cl.C1COCC1>[C:1]([Si:5]([O:6][CH:7]1[CH2:11][CH2:12][CH:13]2[CH2:14][O:15][C:16]3[C:21]([C:22]2([S:23]([C:26]2[CH:27]=[CH:28][C:29]([Cl:32])=[CH:30][CH:31]=2)(=[O:24])=[O:25])[CH2:9][CH2:8]1)=[C:20]([F:33])[CH:19]=[CH:18][C:17]=3[F:34])([CH3:36])[CH3:35])([CH3:2])([CH3:4])[CH3:3]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 23665647Potassium tert-butoxideHCID 67006224HCID 67006224, compound

Product 1

HCID 67006489HCID 67006489, compoundYield 99.1%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 3-(tert-butyl-dimethyl-silanyloxy)-5-[4-(4-chloro-benzenesulfonyl)-5,8-difluoro-chroman-3-yl]-pentan-1-ol (730 mg, 1.30 mmol) in CH2Cl2 (10 mL) at 0° C. was treated with Et3N (360 μL, 2.6 mmol) followed by MsCl (150 μL, 1.95 mmol). After 30 min, the reaction mixture was quenched with saturated aqueous NH4Cl and extracted with CH2Cl2 (2×). The combined organic extracts were washed with saturated aqueous NaHCO3, dried over MgSO4 and concentrated in vacuo to provide the crude product. The residue was dissolved in THF (13 mL), cooled to 0° C. and treated with KOt-Bu (1 M in THF, 3.0 mL, 3.0 mmol). After 1 h, the reaction mixture was quenched with saturated aqueous NH4Cl and extracted with EtOAc (2×). The combined organic extracts were washed with saturated aqueous NaHCO3, brine, dried over MgSO4 and concentrated in vacuo to give the title compound (700 mg, 99% over 2 steps): 1H NMR (CDCl3 400 MHz) δ 7.63 (dd, J=8.8, 1.5 Hz, 2H), 7.49 (dd, J=8.8, 1.5 Hz, 2H), 7.04 (m, 1H), 6.43 (m, 1H), 5.07 (dd, J=10.9, 2.2 Hz, 1H), 4.23 (m, 1H), 4.04 (m, 0.5H), 3.58 (m, 0.5H), 2.97 (m, 1H), 2.71-2.26 (m, 2H), 2.10 (m, 1H), 1.83-1.43 (m, 5H), 0.90 (s, 4.5H), 0.77 (s, 4.5H), 0.03 (s, 3H), −0.01 (s, 3H).

Workup

  1. customthe reaction mixture was quenched with saturated aqueous NH4Cl
  2. extractionextracted with CH2Cl2 (2×)
  3. washThe combined organic extracts were washed with saturated aqueous NaHCO3
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated in vacuo
  6. customto provide the crude product
  7. waitAfter 1 h
  8. customthe reaction mixture was quenched with saturated aqueous NH4Cl
  9. extractionextracted with EtOAc (2×)
  10. washThe combined organic extracts were washed with saturated aqueous NaHCO3, brine
  11. dry with materialdried over MgSO4
  12. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-a2c71aedf7684515880e4ba18ff7662e
Source dataset
uspto-grants-2011_11
Patent number
US08067621B2

Reaction notes

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