Tert-Butylamine → (S)-[2-(4-Benzyloxy-phenyl)-1-(tert-butylamino-methyl)-ethyl]-carbamic acid tert-butyl ester

HRID 278887Notes

Reaction equation

HRID 278887 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].[C:27]([NH2:31])([CH3:30])([CH3:29])[CH3:28].C([BH3-])#N.[Na+]>CO>[C:1]([O:5][C:6](=[O:7])[NH:8][C@H:9]([CH2:25][NH:31][C:27]([CH3:30])([CH3:29])[CH3:28])[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 6385Tert-ButylamineHCID 5003444Sodium cyanoborohydrideHCID 7015729Boc-Tyr(Bzl)-aldehyde

Product 1

HCID 70089277(S)-[2-(4-Benzyloxy-phenyl)-1-(tert-butylamino-methyl)-ethyl]-carbamic acid tert-butyl esterYield 18.3%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Procedure

A solution consisting of 2.86 g (8 mmol) N-tert-butoxycarbonyl-O-benzyl-L-tyrosinal (Example 4, Step A) and 0.846 mL (8 mmol) tert-butyl amine (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 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 a pale amber oil which was chromatographed on a silica gel column using 1% to 2% methanol in ethyl acetate as eluant to give 604 mg (18%) of the title compound as waxy white crystals; mp 77-79° 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 pale amber oil which
  9. customwas chromatographed on a silica gel column

Sources & evidence

ORD record
ord-31749ddce91b4212b2cce862aab4a40e
Source dataset
uspto-grants-2002_03
Patent number
US06362174B1

Reaction notes

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