Diethylamine → (S)-[1-(4-benzyloxy-benzyl)-2-diethylamino-ethyl]-carbamic acid tert-butyl ester

HRID 429131Notes

Reaction equation

HRID 429131 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].[CH2:27]([NH:29][CH2:30][CH3:31])[CH3:28].C([BH3-])#N.[Na+]>CO>[C:1]([O:5][C:6](=[O:7])[NH:8][C@@H:9]([CH2:10][C:11]1[CH:12]=[CH:13][C:14]([O:17][CH2:18][C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=2)=[CH:15][CH:16]=1)[CH2:25][N:29]([CH2:30][CH3:31])[CH2:27][CH3:28])([CH3:3])([CH3:4])[CH3:2]

Participants

5

Reactant 3

HCID 8021DiethylamineHCID 5003444Sodium cyanoborohydrideHCID 7015729Boc-Tyr(Bzl)-aldehyde

Product 1

HCID 59973359(S)-[1-(4-benzyloxy-benzyl)-2-diethylamino-ethyl]-carbamic acid tert-butyl esterYield 7.2%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Procedure

A solution consisting of 2.86 g (8 mmol) N-tert-butoxycarbonyl-O-benzyl-L-tyrosinal (Example 3, Step B) and 0.832 mL (8 mmol) diethyl amine 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 48 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 an amber oil which was chromatographed on a silica gel column using 50:50:1 ethyl acetate:hexane:methanol as eluant to give 236 mg (7%) of (S)-[1-(4-benzyloxy-benzyl)-2-diethylamino-ethyl]-carbamic acid tert-butyl ester as a clear, colorless oil.

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 an amber oil which
  9. customwas chromatographed on a silica gel column

Sources & evidence

ORD record
ord-0f094305f3804df191b8551acd01e253
Source dataset
uspto-grants-2001_11
Patent number
US06316440B1

Reaction notes

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