Phenol → (R)-N-Boc-1-phenoxy-2-propanamine

HRID 2041136Notes

Reaction equation

HRID 2041136 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]([CH3:12])[CH2:10][OH:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:13]1(O)[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C>C1COCC1.O>[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH2:10][O:11][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[CH3:12])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 996PhenolHCID 11776TriphenylphosphineHCID 5363146Diisopropyl azodicarboxylateHCID 13200309tert-butyl N-((2R)-1-hydroxypropan-2-yl)carbamate

Product 1

HCID 10586857(R)-N-Boc-1-phenoxy-2-propanamineYield 14%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

Dissolve (R)-(+)-2-(tert-butoxycarbonylamino)-1-propanol (1.75 g, 10 mmol) and phenol (0.95 g, 10 mmol) in anhydrous THF (75 mL). Cool to 0° C., add triphenylphosphine (4.0 g, 15 mmol) and diisopropylazodicarboxylate dropwise and stir at ambient temperature for 18 h. Pour the mixture into water (300 mL), basify to pH 10 with 5N aqueous NaOH, and extract with ethyl ether (3×100 mL). Wash the organic phase with brine, dry over MgSO4, filter and concentrate. Purify by chromatography on silica gel eluting with hexane/EtOAc (9:1) to give the desired intermediate as an off-white solid (340 mg, 14%).

Workup

  1. extractionbasify to pH 10 with 5N aqueous NaOH, and extract with ethyl ether (3×100 mL)
  2. washWash the organic phase with brine
  3. dry with materialdry over MgSO4
  4. filtrationfilter
  5. concentrationconcentrate
  6. customPurify by chromatography on silica gel eluting with hexane/EtOAc (9:1)

Sources & evidence

ORD record
ord-e52a0a46f7ab497d8314097b340e9e66
Source dataset
uspto-grants-2013_11
Patent number
US08580780B2

Reaction notes

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