4-Methylmorpholine → (S)-tert-Butyl (1-([1,1'-biphenyl]-4-yl)-3-hydroxypropan-2-yl)carbamate

HRID 327618Notes

Reaction equation

HRID 327618 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH2:13][C:14]1[CH:19]=[CH:18][C:17]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)=[CH:16][CH:15]=1)[C:10](O)=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].CN1CCOCC1.ClC(OCC(C)C)=O>C(COC)OC>[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH2:13][C:14]1[CH:15]=[CH:16][C:17]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)=[CH:18][CH:19]=1)[CH2:10][OH:11])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 2761796N-alpha-t-Butyloxycarbonyl-L-biphenylalanine (Boc-L-Bip-OH)

Product 1

HCID 54340554(S)-tert-Butyl (1-([1,1'-biphenyl]-4-yl)-3-hydroxypropan-2-yl)carbamate

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent

Procedure

Similarly to a method reported in Tetrahedron Lett., 1991, 923, to a stirred solution of (S)-2-t-butoxycarbonylamino-3-(biphenyl-4-yl)-propionic acid (3 g, 8.8 mmol) in dimethoxyethane (DME; 8 mL) at -15° is added N-methylmorpholine (0.975 mL, 8.8 mmol), followed by isobutyl chloroformate (1.2 mL, 9.25 mmol). After 5 minutes, the precipitate is removed by filtration and washed with DME (5 mL). The filtrate is cooled to 0° and treated at once with a freshly prepared clear solution of sodium borohydride (500 mg) in water (5 mL). After the strong evolution of gas has ceased, water (100 mL) is added and the product is extracted in ethyl acetate. The organic layer is separated, dried over magnesium sulfate, decolorized with activated charcoal, filtered and concentrated in vacuo to yield (S)-2-(t-butoxycarbonylamino)-3-(biphenyl-4-yl)-propan-1-ol as a white solid, m.p.: 116°, [α]D =-22.90 (c 0.74, MeOH).

Workup

  1. customthe precipitate is removed by filtration
  2. washwashed with DME (5 mL)
  3. temperatureThe filtrate is cooled to 0°
  4. additiontreated at once with a freshly prepared clear solution of sodium borohydride (500 mg) in water (5 mL)
  5. additionwater (100 mL) is added
  6. extractionthe product is extracted in ethyl acetate
  7. customThe organic layer is separated
  8. dry with materialdried over magnesium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-0b0c606f30f54d59828a965a74ac147a
Source dataset
uspto-grants-1993_12
Patent number
US05273990

Reaction notes

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