Phenol → tert-butyl ((3R)-3-hydroxy-3-(3-((tetrahydro-2H-thiopyran-3-yl)methoxy)phenyl)propyl)carbamate

HRID 2277046Notes

Reaction equation

HRID 2277046 reaction equation
C([O-])([O-])=O.[K+].[K+].C1(O)C=CC=CC=1.[OH:14][C@@H:15]([C:26]1[CH:31]=[CH:30][CH:29]=[C:28]([OH:32])[CH:27]=1)[CH2:16][CH2:17][NH:18][C:19](=[O:25])[O:20][C:21]([CH3:24])([CH3:23])[CH3:22].CC1C=CC(S(O[CH2:44][CH:45]2[CH2:50][CH2:49][CH2:48][S:47][CH2:46]2)(=O)=O)=CC=1>CN(C=O)C>[OH:14][C@@H:15]([C:26]1[CH:31]=[CH:30][CH:29]=[C:28]([O:32][CH2:44][CH:45]2[CH2:50][CH2:49][CH2:48][S:47][CH2:46]2)[CH:27]=1)[CH2:16][CH2:17][NH:18][C:19](=[O:25])[O:20][C:21]([CH3:24])([CH3:23])[CH3:22]

Participants

6

Reactant 4

HCID 996PhenolHCID 11430Potassium CarbonateHCID 90405310(R)-tert-butyl 3-hydroxy-3-(3-hydroxyphenyl)propylcarbamateHCID 90405933(tetrahydro-2H-thiopyran-3-yl)methyl 4-methylbenzenesulfonate

Product 1

HCID 131733435tert-butyl ((3R)-3-hydroxy-3-(3-((tetrahydro-2H-thiopyran-3-yl)methoxy)phenyl)propyl)carbamate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

K2CO3 (0.72 g, 5.24 mmol) and phenol (7, Intermediate I) (0.3 g, 1.05 mmol) were added to a solution of (tetrahydro-2H-thiopyran-3-yl)methyl 4-methylbenzenesulfonate (0.29 g, 1.10 mmol) in DMF (10 mL). The reaction mixture was heated at 100° C. under reflux overnight and then cooled. The reaction mixture was extracted with EtOAc, organic layer was dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by flash chromatography (EtOAc:hexane 10-40% gradient) gave tert-butyl ((3R)-3-hydroxy-3-(3-((tetrahydro-2H-thiopyran-3-yl)methoxy)phenyl)propyl)carbamate as a light green solid. Yield (0.21 g, 52%); 1H NMR (400 MHz, CDCl3): δ 7.24 (t, J=8.0 Hz, 1H), 6.91 (d, J=8.0 Hz, 2H), 6.78 (d, 1H), 4.87 (bs, 1H), 4.71 (bs, 1H), 3.84-3.80 (m, 2H), 3.49 (bs, 1H), 3.21-3.13 (m, 2H), 2.82-2.77 (m, 1H), 2.62-2.47 (m, 3H), 2.18 (bs, 1H), 2.08-2.04 (m, 1H), 1.91-1.74 (m, 4H), 1.45 (s, 9H), 1.30-1.20 (m, 3H); MS: m/z 382.2 [M+H]+.

Workup

  1. temperatureunder reflux overnight
  2. temperaturecooled
  3. extractionThe reaction mixture was extracted with EtOAc, organic layer
  4. dry with materialwas dried over anhydrous Na2SO4
  5. concentrationconcentrated under reduced pressure
  6. customPurification by flash chromatography (EtOAc:hexane 10-40% gradient)

Sources & evidence

ORD record
ord-de8322f951dc4b978f5f94b347e43e3f
Source dataset
uspto-grants-2015_09
Patent number
US09133154B2

Reaction notes

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