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

HRID 911249Notes

Reaction equation

HRID 911249 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-f99b7eb6ff234c8996f6ab37f3679837
Source dataset
uspto-grants-2011_09
Patent number
US08022062B2

Reaction notes

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