Morpholine → [2-(4-Benzyloxy-phenyl)-1-morpholin-4-ylmethyl-ethyl]-carbamic acid tert-butyl ester

HRID 429129Notes

Reaction equation

HRID 429129 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]([CH:25]=O)[CH2:10][C:11]1[CH:16]=[CH:15][C:14]([O:17][CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[CH:13][CH:12]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[NH:27]1[CH2:32][CH2:31][O:30][CH2:29][CH2:28]1.C([BH3-])#N.[Na+]>CO>[C:1]([O:5][C:6](=[O:7])[NH:8][CH:9]([CH2:25][N:27]1[CH2:32][CH2:31][O:30][CH2:29][CH2:28]1)[CH2:10][C:11]1[CH:12]=[CH:13][C:14]([O:17][CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[CH:15][CH:16]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 8083MorpholineHCID 5003444Sodium cyanoborohydrideHCID 7015729Boc-Tyr(Bzl)-aldehyde

Product 1

HCID 18711796[2-(4-Benzyloxy-phenyl)-1-morpholin-4-ylmethyl-ethyl]-carbamic acid tert-butyl esterYield 45%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Procedure

A solution consisting of 2.86 g (8 mmol) N-tert-butoxycarbonyl-O-benzyl-L-tyrosinal and 0.701 mL (8 mmol) morpholine (Aldrich, Milwaukee, Wis.) in 36 mL methanol containing 1% acetic acid was stirred at 25° C. for 20 minutes, at which time a solution of 1.06 g (16 mmol) sodium cyanotrihydridoborate (Aldrich, Milwaukee, Wis.) in 12 mL methanol was added and the resulting mixture stirred for 24 hours. The reaction was quenched by the addition of 3 M HCl in 3 mL increments until the vigorous bubbling subsided. The mixture was neutralized with saturated NaHCO3 solution then extracted with three 100 mL portions of ethyl acetate. The combined extracts were washed with 100 mL brine, dried over anhydrous sodium sulphate, and evaporated at reduced pressure to give a clear, colorless oil which was chromatographed on a silica gel column using ethyl acetate:hexane, 1:1 as eluant. The A white, waxy solid was recrystallized from 2,2,4-trimethylpentane to give 1.53 g (45%) of [2-(4-benzyloxy-phenyl)-1-morpholin-4-ylmethyl-ethyl]-carbamic acid tert-butyl ester as soft white crystals; mp 98-99° C.

Workup

  1. additionwas added
  2. customThe reaction was quenched by the addition of 3 M HCl in 3 mL increments until the
  3. customvigorous bubbling
  4. extractionthen extracted with three 100 mL portions of ethyl acetate
  5. washThe combined extracts were washed with 100 mL brine
  6. dry with materialdried over anhydrous sodium sulphate
  7. customevaporated at reduced pressure
  8. customto give a clear, colorless oil which
  9. customwas chromatographed on a silica gel column
  10. customThe A white, waxy solid was recrystallized from 2,2,4-trimethylpentane

Sources & evidence

ORD record
ord-20966589541c43e7b7f9a9e275ffc964
Source dataset
uspto-grants-2001_11
Patent number
US06316440B1

Reaction notes

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