9-Fluorenylmethyl chloroformate → 3-({[(9H-fluoren-9-yl)methoxy]carbonyl}amino)-2,2-dimethylpropanoic acid

HRID 74763

Reaction equation

HRID 74763 reaction equation
Cl.[NH2:2][CH2:3][C:4]([CH3:9])([CH3:8])[C:5]([OH:7])=[O:6].C(N(C(C)C)CC)(C)C.[CH:19]1[C:31]2[CH:30]([CH2:32][O:33][C:34](Cl)=[O:35])[C:29]3[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=3)[C:23]=2[CH:22]=[CH:21][CH:20]=1>ClCCl>[CH:19]1[C:31]2[CH:30]([CH2:32][O:33][C:34]([NH:2][CH2:3][C:4]([CH3:9])([CH3:8])[C:5]([OH:7])=[O:6])=[O:35])[C:29]3[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=3)[C:23]=2[CH:22]=[CH:21][CH:20]=1

Participants

5

Reactant 3

HCID 343679-Fluorenylmethyl chloroformateHCID 81531DiisopropylethylamineHCID 534077243-Amino-2,2-dimethylpropanoic acid hydrochloride

Product 1

HCID 450244313-({[(9H-fluoren-9-yl)methoxy]carbonyl}amino)-2,2-dimethylpropanoic acidYield 45.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To 3-amino-2,2-dimethylpropanoic acid, hydrochloride salt (250 mg, 1.63 mmol, 1 eq.) in dichloromethane (4 mL, 0.4 M) was added diisopropylethylamine (859 μL, 4.88 mmol, 3 eq.) followed by (9H-fluoren-9-ylmethoxy)carbonyl chloride (473 mg, 1.79 mmol, 1.1 eq.) The reaction was stirred for 18 hours and then concentrated in vacuo. The residue was taken up in ethyl acetate (3 mL) and washed with 1 M aqueous hydrochloric acid solution (2×1 mL) and with brine. The organic layer was dried over sodium sulfate, filtered, and purified by silica gel chromatography (Gradient: 0% to 100% ethyl acetate in heptane) to give #93 (250 mg, 45%) as an oil. 1H NMR (400 MHz, DMSO-d6) δ 12.22 (s, 1H), 7.89 (d, J=7.4 Hz, 2H), 7.72 (d, J=7.4 Hz, 2H), 7.38-7.44 (m, 2H), 7.27-7.35 (m, 3H), 4.18-4.30 (m, 3H), 3.16 (d, J=6.2 Hz, 2H), 1.05 (s, 6H).

Workup

  1. concentrationconcentrated in vacuo
  2. washwashed with 1 M aqueous hydrochloric acid solution (2×1 mL) and with brine
  3. dry with materialThe organic layer was dried over sodium sulfate
  4. filtrationfiltered
  5. custompurified by silica gel chromatography (Gradient: 0% to 100% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-e69ad027905349daab7a1ad374bc14e2
Source dataset
uspto-grants-2014_09
Patent number
US08828401B2

Linked notes

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