Phenol → HCID 68718986, compound

HRID 2246705Notes

Reaction equation

HRID 2246705 reaction equation
[C:1]([O:5][C:6]([NH:8][CH2:9][C@@H:10]([OH:22])[CH2:11][P:12]([CH2:15][CH:16]1[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]1)(=[O:14])[OH:13])=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:23]1(O)[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.C(N(CC)CC)C>C1COCC1.C(OCC)(=O)C>[C:23]1([O:14][P:12]([CH2:11][C@H:10]([OH:22])[CH2:9][NH:8][C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])([CH2:15][CH:16]2[CH2:17][CH2:18][CH2:19][CH2:20][CH2:21]2)=[O:13])[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1

Participants

6

Reactant 3

HCID 996PhenolHCID 8471TriethylamineHCID 68623216HCID 68623216, compound

Product 1

HCID 68718986HCID 68718986, compoundYield 61%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of ((R)-3-tert-butoxycarbonylamino-2-hydroxy-propyl)-cyclohexylmethyl-phosphinic acid (0.67 g, 2.0 mmol) in 10 mL THF at 0° C. was added 1-chloro-N, N-2-trimethyl-1-propenylamine (319 mg, 2.4 mmol). After stirring for 10 min at 0° C., a solution of phenol (188 mg, 2.0 mmol) and triethylamine (243 mg, 2.4 mmol) in THF (3 mL) was added dropwise. After addition the reaction mixture was stirred at 0° C. for 2 h and then room temperature for 16 h. The reaction was diluted with ethyl acetate and washed with water and brine. The organic layer was dried with magnesium sulfate, filtered and concentrated in vacuo to give the crude product. Purification by gradient flash chromatography (methanol/methylene chloride) on a 35 g RediSep disposable column gave ((R)-3-tert-butoxycarbonylamino-2-hydroxy-propyl)-cyclohexylmethyl-phosphinic acid phenyl ester (500 mg, 1.22 mmol). 1H-NMR (CDCl3, 300 MHz): δ 7.35 (m, 2H), 7.18 (m, 3H), 4.18 (br s, H), −33.21-3.09 (m, 2H), 2.01-1.58 (m, 10H), 1.43-0.95 (m, 15H). 31P NMR (CD3OD, 300 MHz): 57.90, 58.65.

Workup

  1. additionAfter addition the reaction mixture
  2. stirringwas stirred at 0° C. for 2 h
  3. waitroom temperature for 16 h
  4. washwashed with water and brine
  5. dry with materialThe organic layer was dried with magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customto give the crude product
  9. customPurification by gradient flash chromatography (methanol/methylene chloride) on a 35 g RediSep disposable column

Sources & evidence

ORD record
ord-e53351f0b5164968b954a4b3a3449ef9
Source dataset
uspto-grants-2010_03
Patent number
US07687540B2

Reaction notes

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